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Understanding Breast Cancer What Is Breast Cancer?
What Is Breast Cancer?

Last modified on September 18, 2012 at 10:19 am
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Breast cancer is an uncontrolled growth of breast cells. To better understand breast

cancer, it helps to understand how any cancer can develop.
Cancer occurs as a result of mutations, or abnormal changes, in the genes responsible for
regulating the growth of cells and keeping them healthy. The genes are in each cells nucleus,
which acts as the control room of each cell. Normally, the cells in our bodies replace
themselves through an orderly process of cell growth: healthy new cells take over as old ones
die out. But over time, mutations can turn on certain genes and turn off others in a cell.
That changed cell gains the ability to keep dividing without control or order, producing more
cells just like it and forming a tumor.
A tumor can be benign (not dangerous to health) or malignant (has the potential to be
dangerous). Benign tumors are not considered cancerous: their cells are close to normal in
appearance, they grow slowly, and they do not invade nearby tissues or spread to other parts
of the body. Malignant tumors are cancerous. Left unchecked, malignant cells eventually can
spread beyond the original tumor to other parts of the body.
The term breast cancer refers to a malignant tumor that has developed from cells in
the breast. Usually breast cancer either begins in the cells of the lobules, which are the milkproducing glands, or the ducts, the passages that drain milk from the lobules to the nipple.
Less commonly, breast cancer can begin in the stromal tissues, which include the fatty and
fibrous connective tissues of the breast.
Breast AnatomyLarger Version

Over time, cancer cells can invade nearby healthy breast tissue and make their way into the
underarm lymph nodes, small organs that filter out foreign substances in the body. If cancer
cells get into the lymph nodes, they then have a pathway into other parts of the body. The
breast cancers stage refers to how far the cancer cells have spread beyond the original tumor
(see Stages of Breast Cancer table for more information).
Breast cancer is always caused by a genetic abnormality (a mistake in the genetic material).
However, only 5-10% of cancers are due to an abnormality inherited from your mother or
father. About 90% of breast cancers are due to genetic abnormalities that happen as a result
of the aging process and the wear and tear of life in general.
There are steps every person can take to help the body stay as healthy as possible and lower
risk of breast cancer or a breast cancer recurrence (such as maintaining a healthy weight, not
smoking, limiting alcohol, and exercising regularly). Learn what you can do to manage breast
cancer risk factors.
Always remember, breast cancer is never anyone's fault. Feeling guilty, or telling yourself
that breast cancer happened because of something you or anyone else did, is not productive.
Stages of Breast Cancer

Stage Definition
Cancer cells remain inside the breast duct, without invasion into normal adjacent
Stage 0
breast tissue.
The tumor measures up to 2 cm
Stage
AND
IA
the cancer has not spread outside the breast; no lymph nodes are involved
There is no tumor in the breast; instead, small groups of cancer cells -- larger than 0.2
millimeter but not larger than 2 millimeters are found in the lymph nodes
Stage OR
IB
there is a tumor in the breast that is no larger than 2 centimeters, and there are small
groups of cancer cells larger than 0.2 millimeter but not larger than 2 millimeters
in the lymph nodes.
No tumor can be found in the breast, but cancer cells are found in the axillary lymph
nodes (the lymph nodes under the arm)
OR
Stage the tumor measures 2 centimeters or smaller and has spread to the axillary lymph
IIA
nodes
OR
the tumor is larger than 2 but no larger than 5 centimeters and has not spread to the
axillary lymph nodes.
The tumor is larger than 2 but no larger than 5 centimeters and has spread to the
Stage axillary lymph nodes
IIB
OR
the tumor is larger than 5 centimeters but has not spread to the axillary lymph nodes.
No tumor is found in the breast. Cancer is found in axillary lymph nodes that are
sticking together or to other structures, or cancer may be found in lymph nodes near
the breastbone
Stage
OR
IIIA
the tumor is any size. Cancer has spread to the axillary lymph nodes, which are
sticking together or to other structures, or cancer may be found in lymph nodes near
the breastbone.
The tumor may be any size and has spread to the chest wall and/or skin of the breast
Stage
AND
IIIB
may have spread to axillary lymph nodes that are clumped together or sticking to
other structures, or cancer may have spread to lymph nodes near the breastbone.
Stage
IIIC
Stage
IV
Inflammatory breast cancer is considered at least stage IIIB.

There may either be no sign of cancer in the breast or a tumor may be any size and
may have spread to the chest wall and/or the skin of the breast
AND
the cancer has spread to lymph nodes either above or below the collarbone
AND
the cancer may have spread to axillary lymph nodes or to lymph nodes near the
breastbone.
The cancer has spread or metastasized to other parts of the body.
Statistic
About 1 in 8 U.S. women (just under 12%) will develop invasive breast cancer over
the course of her lifetime.
In 2011, an estimated 230,480 new cases of invasive breast cancer were expected to
be diagnosed in women in the U.S., along with 57,650 new cases of non-invasive (in
situ) breast cancer.
About 2,140 new cases of invasive breast cancer were expected to be diagnosed in
men in 2011. A mans lifetime risk of breast cancer is about 1 in 1,000.
From 1999 to 2005, breast cancer incidence rates in the U.S. decreased by about 2%
per year. The decrease was seen only in women aged 50 and older. One theory is that
this decrease was partially due to the reduced use of hormone replacement therapy
(HRT) by women after the results of a large study called the Womens Health
Initiative were published in 2002. These results suggested a connection between HRT
and increased breast cancer risk.
About 39,520 women in the U.S. were expected to die in 2011 from breast cancer,
though death rates have been decreasing since 1990 especially in women under 50.
These decreases are thought to be the result of treatment advances, earlier detection
through screening, and increased awareness.
For women in the U.S., breast cancer death rates are higher than those for any other
cancer, besides lung cancer.
Besides skin cancer, breast cancer is the most commonly diagnosed cancer among
American women. Just under 30% of cancers in women are breast cancers.
White women are slightly more likely to develop breast cancer than AfricanAmerican women. However, in women under 45, breast cancer is more common in
African-American women than white women. Overall, African-American women are
more likely to die of breast cancer. Asian, Hispanic, and Native-American women
have a lower risk of developing and dying from breast cancer.
In 2011, there were more than 2.6 million breast cancer survivors in the US.
A womans risk of breast cancer approximately doubles if she has a first-degree

relative (mother, sister, daughter) who has been diagnosed with breast cancer. About
15% of women who get breast cancer have a family member diagnosed with it.
About 5-10% of breast cancers can be linked to gene mutations (abnormal changes)
inherited from ones mother or father. Mutations of the BRCA1 and BRCA2 genes
are the most common. Women with these mutations have up to an 80% risk of
developing breast cancer during their lifetime, and they are more likely to be
diagnosed at a younger age (before menopause). An increased ovarian cancer risk is
also associated with these genetic mutations.
In men, about 1 in 10 breast cancers are believed to be due to BRCA2 mutations, and
even fewer cases to BRCA1 mutations.
About 85% of breast cancers occur in women who have no family history of breast
cancer. These occur due to genetic mutations that happen as a result of the aging
process and life in general, rather than inherited mutations.
The most significant risk factors for breast cancer are gender (being a woman) and
age (growing older).
As of Jan. 1, 2009, there were about 2,747,459 women alive in the United States with
a history of breast cancer. This includes women being treated and women who are
disease-free.
Understanding Breast Cancer Breast Cancer Risk and Risk Factors
Breast Cancer Risk and Risk Factors

Last modified on September 17, 2012 at 6:55 pm
By now you may be familiar with the statistic that says 1 in 8 women will develop invasive
breast cancer. Many people misinterpret this to mean that, on any given day, they and the
women they know have a 1-in-8 risk of developing the disease. Thats simply not true.
In reality, about 1 in 8 women in the United States 12%, or about 12 out of every 100
can expect to develop breast cancer over the course of an entire lifetime. In the U.S., an
average lifetime is about 80 years. So, its more accurate to say that 1 in 8 women in the U.S.
who reach the age of 80 can expect to develop breast cancer. In each decade of life, the risk
of getting breast cancer is actually lower than 12% for most women.
People tend to have very different ways of viewing risk. For you, a 1-in-8 lifetime risk may
seem like a high likelihood of getting breast cancer. Or you may turn this around and reason
that there is a 7-in-8, or 87.5%, chance you will never get breast cancer, even if you live to
age 80. How you view risk often depends on your individual situation for example,
whether you or many women you know have had breast cancer, or you have reason to believe
you are at higher-than-normal risk for the disease and your usual way of looking at the
world.
Even though studies have found that women have a 12% lifetime risk of developing breast
cancer, your individual risk may be higher or lower than that. Individual risk is affected by
many different factors, such as family history, reproductive history, lifestyle, environment,
and others.
For more information on understanding breast cancer risk and risk factors, visit the Lower
Your Risk section of Breastcancer.org.
This section is designed to help you better understand breast cancer risk and some of the
factors that can increase risk.
Risk of Developing Breast Cancer

Breast Cancer Risk Factors
Risk of Developing Breast Cancer

The term risk is used to refer to a number or percentage that describes how likely a certain
event is to occur. When we talk about factors that can increase or decrease the risk of
developing breast cancer, either for the first time or as a recurrence, we often talk about two
different types of risk: absolute risk and relative risk.
Absolute risk
Absolute risk is used to describe an individuals likelihood of developing breast cancer.
It is based on the number of people who will develop breast cancer within a certain time
period. Absolute risk also can be stated as a percentage.
When we say that 1 in 8 women in the United States, or 12%, will develop breast cancer over
the course of a lifetime, we are talking about absolute risk. On average, an individual woman
has a 1-in-8 chance of developing breast cancer over an 80-year lifespan.
The absolute risk of developing breast cancer during a particular decade of life is lower than
1 in 8. The younger you are, the lower the risk. For example:
From age 30 to 39, absolute risk is 1 in 233, or 0.43%. This means that 1 in 233
women in this age group can expect to develop breast cancer. Put another way, your
odds of developing breast cancer if you are in this age range are 1 in 233.
From age 40 to 49, absolute risk is 1 in 69, or 1.4%.
As you can see, the older you are, the higher your absolute risk of breast cancer. Keep in
mind that these numbers and percentages are averages for the whole population. Your
individual breast cancer risk may be higher or lower, depending on a number of factors,
including family history, reproductive history (such as menstrual and childbearing history),
race/ethnicity, and other factors.
Take family history, for example. The absolute risk of breast cancer is much higher for
women who have inherited mutations in the genes known as BRCA1 or BRCA2. Their
absolute risk over the course of a lifetime ranges from 40-85%. This means that out of every
100 women who have these mutations, anywhere from 40 to 85 of them can expect to
develop breast cancer should they live to age 80.
If you have breast cancer, absolute risk also can be used to describe the likelihood of a
certain treatment outcome or the course of the disease. For example, suppose that, based
on the characteristics of the breast cancer (stage, grade, other test results), your age and
medical history, and the treatments you have, your doctor tells you that your likelihood of
disease-free survival at 5 years being alive with no evidence of breast cancer is 90%.
This means that your absolute risk of having the breast cancer come back within 5 years is
10%, or 1 in 10. In other words, 1 out of 10 women with similar characteristics and the same
treatment plan can expect to have a recurrence within that time frame. Nine out of 10, or
90%, would not.
Relative risk
Relative risk is a number or percentage that compares one groups risk of developing
breast cancer to anothers. This is the type of risk frequently reported by research studies,
which often compare groups of women with different characteristics or behaviors to
determine whether one group has a higher or lower risk of breast cancer than the other (either
as a first-time diagnosis or recurrence).
Understanding relative risk can help you answer an important question: If I make certain
lifestyle choices or have certain treatments, how much will I increase or decrease my risk of
developing breast cancer or having a recurrence?
Example of breast cancer risk going up

Many studies have shown that women who have two or more alcoholic drinks each day have
a higher risk of developing breast cancer. (A drink is defined as 12 ounces of regular beer, 5
ounces of wine, or 1.5 ounces of 80-proof liquor.) You may hear this relative risk described
as a percentage or a number:
Compared to women who do not drink, women who have two or more drinks per day
have a 25% higher risk of breast cancer. Put another way, they are 25% more
likely to develop breast cancer over the course of a lifetime than nondrinkers are.
This doesnt mean that their lifetime risk of getting breast cancer is 25% it means
that their risk of getting breast cancer is 25% higher relative to people who dont
drink. This percentage is how you are likely to see relative risk reported by television,
the Internet, and newspapers.
Compared to women who do not drink, women who have two or more drinks per day
have a relative risk of 1.25. This number is how researchers and scientific papers
would usually talk about relative risk. The number 1 is assigned to the baseline
group (women who do not drink), since their risk remains the same. The .25
describes the relative increase in risk for the other group; it is another way of
expressing the 25% higher lifetime risk (25% = .25).
Another way of saying this is that women who drink two or more alcoholic drinks per
day have 1.25 (1 + .25 = 1.25) times the risk of developing breast cancer than
women who do not drink.
Relative risk can be a tricky concept, because most people tend to focus on the reported
percentage e.g., 25% higher risk which sounds alarming. Yes, a 25% higher risk of
developing breast cancer (relative to people who dont drink) is significant, but it doesnt tell
a woman what her lifetime risk is if she drinks two or more alcoholic drinks per day for the
rest of her life. Since women in this group have 1.25 times the risk of developing breast
cancer, its necessary to multiply the absolute risk of breast cancer (12%) for women in the
general population (13%, or .13) by relative risk (1.25):
.127 x 1.25 = .159. This means that a womans absolute lifetime risk of developing
breast cancer if she drinks two or more alcoholic drinks per day is just under 16%,
versus 12% for women who do not drink.
Many different factors can increase and/or decrease your risk of developing breast cancer.
Online tools such as the National Cancer Institutes Breast Cancer Risk Assessment Tool
allow you to input individual information to calculate your risk.
Example of breast cancer risk going down

Suppose you have had breast cancer and undergone lumpectomy (removal of the tumor itself
and a margin of healthy surrounding tissue). The absolute risk of the breast cancer coming
back in the same breast is about 25%. But if you have radiation therapy to the remaining
breast tissue, you can reduce that risk by about 60%. To describe this relative risk decrease,
your doctor might say:
Compared to women who have lumpectomy alone, you have a 60% lower risk of
developing breast cancer again in the same breast if you have radiation therapy
after lumpectomy.
Medical researchers might express it this way:
Compared to women who do not have radiation therapy, your relative risk of
developing breast cancer is .40 (1 .60 = .40). Again, the number 1 is assigned
to the baseline group, which is not taking the extra action to decrease the risk. The .
60 is subtracted from 1 because it represents a decrease in risk. In other words, you
have about 40% of the risk of developing breast cancer again in the same breast as
they do.
So in this scenario, what difference does radiation therapy really make for you in terms of
reducing the absolute risk of cancer recurrence in the same breast? To know that, you have to
multiply the risk of recurrence without radiation (25%, or .25) by the relative risk of .40:
.25 X .40 =.10. In this hypothetical situation, your absolute risk of the cancer
returning in the same breast is 10%, or 1 in 10, if you have radiation therapy, versus
about 25%, or 1 in 4, if you dont. Put another way, 1 in 10 women who have
radiation therapy can expect to experience recurrence in the same breast, versus 1
in 4 women who do not have the treatment.
So, relative risk is the number that tells you how much something you do, such as a certain
behavior or treatment, can change your risk for breast cancer compared to those who dont do
it. A relative risk of:
.5 means that your risk decreases by half, or 50%

1.88 means that your risk increases by 88%
3.0 means that your risk triples, or goes up by 300% (you have three times the risk)
As the examples above show, knowing how much your breast cancer risk goes up or down
with certain lifestyle factors and treatment options can help you and your doctor make the
best decisions for you. These are hypothetical examples; you can find out more about breast
cancer risk in the Lower Your Risk section.
Breast Cancer Risk Factors

A risk factor is anything that increases your risk of developing breast cancer. Many of the
most important risk factors for breast cancer are beyond your control, such as age, family
history, and medical history. However, there are some risk factors you can control, such as
weight, physical activity, and alcohol consumption.
Be sure to talk with your doctor about all of your possible risk factors for breast cancer. There
may be steps you can take to lower your risk of breast cancer, and your doctor can help you
come up with a plan. Your doctor also needs to be aware of any other risk factors beyond
your control, so that he or she has an accurate understanding of your level of breast cancer
risk. This can influence recommendations about breast cancer screening what tests to have
and when to start having them.
Risk factors you can control

Weight. Being overweight is associated with increased risk of breast cancer, especially for
women after menopause. Fat tissue is the bodys main source of estrogen after menopause,
when the ovaries stop producing the hormone. Having more fat tissue means having higher
estrogen levels, which can increase breast cancer risk.
Diet. Diet is a suspected risk factor for many types of cancer, including breast cancer, but
studies have yet to show for sure which types of foods increase risk. Its a good idea to
restrict sources of red meat and other animal fats (including dairy fat in cheese, milk, and ice
cream), because they may contain hormones, other growth factors, antibiotics, and pesticides.
Some researchers believe that eating too much cholesterol and other fats are risk factors for
cancer, and studies show that eating a lot of red and/or processed meats is associated with a
higher risk of breast cancer. A low-fat diet rich in fruits and vegetables is generally
recommended. For more information, visit our page on healthy eating to reduce cancer risk in
the Nutrition section.
Exercise. Evidence is growing that exercise can reduce breast cancer risk. The American
Cancer Society recommends engaging in 45-60 minutes of physical exercise 5 or more days a
week.
Alcohol consumption. Studies have shown that breast cancer risk increases with the amount
of alcohol a woman drinks. Alcohol can limit your livers ability to control blood levels of
the hormone estrogen, which in turn can increase risk.
Smoking. Smoking is associated with a small increase in breast cancer risk.
Exposure to estrogen. Because the female hormone estrogen stimulates breast cell growth,
exposure to estrogen over long periods of time, without any breaks, can increase the risk of
breast cancer. Some of these risk factors are under your control, such as:
taking combined hormone replacement therapy (estrogen and progesterone; HRT) for
several years or more, or taking estrogen alone for more than 10 years
being overweight
regularly drinking alcohol
Recent oral contraceptive use. Using oral contraceptives (birth control pills) appears to
slightly increase a womans risk for breast cancer, but only for a limited period of time.
Women who stopped using oral contraceptives more than 10 years ago do not appear to have
any increased breast cancer risk.
Stress and anxiety. There is no clear proof that stress and anxiety can increase breast cancer
risk. However, anything you can do to reduce your stress and to enhance your comfort, joy,
and satisfaction can have a major effect on your quality of life. So-called mindful measures
(such as meditation, yoga, visualization exercises, and prayer) may be valuable additions to
your daily or weekly routine. Some research suggests that these practices can strengthen the
immune system.
Risk factors you cant control

Gender. Being a woman is the most significant risk factor for developing breast cancer.
Although men can get breast cancer, too, womens breast cells are constantly changing and
growing, mainly due to the activity of the female hormones estrogen and progesterone. This
activity puts them at much greater risk for breast cancer.
Age. Simply growing older is the second biggest risk factor for breast cancer. From age 30 to
39, the risk is 1 in 233, or .43%. That jumps to 1 in 27, or almost 4%, by the time you are in
your 60s.
Family history of breast cancer. If you have a first-degree relative (mother, daughter, sister)
who has had breast cancer, or you have multiple relatives affected by breast or ovarian cancer
(especially before they turned age 50), you could be at higher risk of getting breast cancer.
Personal history of breast cancer. If you have already been diagnosed with breast cancer,
your risk of developing it again, either in the same breast or the other breast, is higher than if
you never had the disease.
Race. White women are slightly more likely to develop breast cancer than are African
American women. Asian, Hispanic, and Native American women have a lower risk of
developing and dying from breast cancer.
Radiation therapy to the chest. Having radiation therapy to the chest area as a child or
young adult as treatment for another cancer significantly increases breast cancer risk. The
increase in risk seems to be highest if the radiation was given while the breasts were still
developing (during the teen years).
Breast cellular changes. Unusual changes in breast cells found during a breast biopsy
(removal of suspicious tissue for examination under a microscope) can be a risk factor for
developing breast cancer. These changes include overgrowth of cells (called hyperplasia) or
abnormal (atypical) appearance.
Exposure to estrogen. Because the female hormone estrogen stimulates breast cell growth,
exposure to estrogen over long periods of time, without any breaks, can increase the risk of
breast cancer. Some of these risk factors are not under your control, such as:
starting menstruation (monthly periods) at a young age (before age 12)

going through menopause (end of monthly cycles) at a late age (after 55)
exposure to estrogens in the environment (such as hormones in meat or pesticides

such as DDT, which produce estrogen-like substances when broken down by the
body)
Pregnancy and breastfeeding. Pregnancy and breastfeeding reduce the overall number of
menstrual cycles in a womans lifetime, and this appears to reduce future breast cancer risk.
Women who have never had a full-term pregnancy, or had their first full-term pregnancy
after age 30, have an increased risk of breast cancer. For women who do have children,
breastfeeding may slightly lower their breast cancer risk, especially if they continue
breastfeeding for 1 1/2 to 2 years. For many women, however, breastfeeding for this long is
neither possible nor practical.
DES exposure. Women who took a medication called diethylstilbestrol (DES), used to
prevent miscarriage from the 1940s through the 1960s, have a slightly increased risk of breast
cancer. Women whose mothers took DES during pregnancy may have a higher risk of breast
cancer as well.
http://www.breastcancer.org/symptoms/understand_bc/risk/factors
This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal
guidelines, when they exist. The article ends with the author's clinical recommendations.
A healthy, 42-year-old white woman wants to discuss breast-cancer screening. She has no
breast symptoms, had menarche at the age of 14 years, gave birth to her first child at the age
of 26 years, is moderately overweight, drinks two glasses of wine most evenings, and has no
family history of breast or ovarian cancer. She has never undergone mammography. She
notes that a friend who maintained the healthiest lifestyle possible is now being treated for
metastatic breast cancer, and she wants to avoid the same fate. What would you advise?
The Clinical Problem

Worldwide, breast cancer is now the most common cancer diagnosed in women and is the
leading cause of deaths from cancer among women, with approximately 1.3 million new
cases and an estimated 458,000 deaths reported in 2008.1 A woman born in the United States
today has a 1 in 8 chance of having invasive breast cancer during her lifetime.2 The risk of
breast cancer increases with age (Figure 1Figure 1

Age-Specific Incidence of
Invasive Breast Cancer per 1000 Women per Year in the United States.) and with other risk
factors (Table 1Table 1
Risk Factors for Breast Cancer.).
Tumor stage remains the most important determinant of the outcome for women with breast
cancer. Among women with nonmetastatic breast cancer, the risk of distant recurrence is
most closely correlated with the number of axillary nodes involved, followed by tumor size.4
Moreover, there is a strong correlation between tumor size and the extent of axillary spread.5
This means that the ideal screening regimen for breast cancer would be one that could detect
a tumor before it was large enough to be palpable.
Since 1990, mortality from breast cancer in the United States and other industrialized
countries has been decreasing at the rate of approximately 2.2% per year.1 In the United
States, this decline has been attributed both to advances in adjuvant therapy and to increasing
use of screening mammography, in approximately equal measure.6 Nevertheless, in contrast
to its 2002 guidelines,7 the more recent recommendations of the U.S. Preventive Services
Task Force (USPSTF), published in November 2009, support a reduction in the use of
screening mammography.8 This revision resulted in considerable confusion and controversy.
The two most disputed changes were the reclassification of screening for women between the
ages of 40 and 49 years from a B recommendation (based on moderately strong evidence) to
a C recommendation (the decision . . . should be an individual one and take into account
patient context, including the patient's values regarding specific benefits and harms), and the
recommendation that the frequency of screening be reduced from every 1 to 2 years to every
2 years.8
This article focuses on the updated evidence and recommendations for screening women who
are at average risk for breast cancer that have been published since this topic was last
reviewed in the Journal, in 2003. It does not address breast-cancer screening for women at
high risk that is, women with a lifetime risk of breast cancer that is greater than 20 to 25%
on the basis of genetic testing, a strong family history (e.g., multiple cases of early-onset
breast cancer, ovarian cancer, or both), or early therapeutic chest irradiation which has
been reviewed previously.9
Strategies and Evidence for Screening

The decision to screen either a particular population or a specific patient for a disease
involves weighing benefits against costs. In the case of breast-cancer screening, the most
important benefits are a reduction in the risk of death and the number of life-years gained.
Costs include the financial costs and other costs of the screening regimen itself (radiation
risk, pain, inconvenience, and anxiety), the ensuing diagnostic workup in the case of false
positive results, and overdiagnosis (the detection of cancer that would never have become
clinically evident). The ratio of benefit to cost varies significantly with the patient's age.8
Women 50 to 69 Years of Age

Screening mammography for women 50 to 69 years of age is universally recommended. All
but one of the trials in the meta-analysis that included women in their 60s showed a
significant reduction in mortality in the screened group, although this was not true for the
subgroup of women in their 50s. Still, a meta-analysis8 revealed significant reductions in the
number of deaths due to breast cancer in both these age groups 14% for women in their
50s and 32% for those in their 60s (Table 2Table 2

Relative Risk of Death
from Breast Cancer, Number Needed to Invite to Screening, and Rates of False Positive and
False Negative Results, According to Age.). The greater reduction among the older group of
women reflects the increasing sensitivity of mammographic testing with age, which is
associated with a decrease in breast density and slower tumor growth. The fact that the
number needed to screen to prevent one death from breast cancer is lower for women in their
60s reflects this higher sensitivity, as well as the higher incidence of breast cancer in this age
group.
Women 70 Years of Age or Older

Data are limited regarding the effects of screening mammography in women who are 70
years of age or older. The only randomized trial that included such women showed no benefit
in this age group (Table 2). In a national screening program in northern Sweden, the relative
risk of death from breast cancer for women 70 to 74 years of age who were invited to
undergo screening, as compared with those not yet invited, was 1.08 (95% confidence
interval [CI], 0.58 to 2.03).18 Using six independent statistical models based on clinical
screening data and cancer outcomes in the United States, the Cancer Intervention and
Surveillance Modeling Network (CISNET) of the National Cancer Institute estimated that
two additional deaths from breast cancer would be prevented per 1000 women screened from
the age of 70 to 74 years, with little additional benefit to be gained from extending screening
beyond 74 years.19 There is agreement that screening is not indicated in women who have
serious coexisting illnesses and a life expectancy of less than 5 to 10 years.
Women 40 to 49 Years of Age

Although no single randomized trial has clearly shown a reduction in mortality from
mammographic screening among women 40 to 49 years of age, several meta-analyses that
included this age group have shown that mortality from breast cancer is significantly reduced
(by 15 to 20%). 20,21 On the basis of these results, as well as those of its own meta-analysis,
which showed that mammography was associated with a relative risk of 0.85 (95% CI, 0.79
to 0.99) for death from breast cancer,17 the USPSTF previously recommended routine
screening mammography for women in this age group.7
Since it had been argued that the benefit of screening women in their 40s could largely be
attributed to the detection of cancers after the age of 50 years in women who had enrolled in
the trials in their late 40s, the Age trial (ISRCTN24647151)14 assessed the effects of
screening among approximately 161,000 women 39 to 41 years of age. Those randomly
assigned to annual mammography until the age of 48 years had a nonsignificant reduction in
the risk of death from breast cancer (relative risk, 0.83; 95% CI, 0.66 to 1.04), and the
relative risk for death from any cause was 0.97 (95% CI, 0.89 to 1.04) at a mean follow-up of
10.7 years (number needed to screen to prevent one death from breast cancer, 2512).
However, this study had several limitations that might have decreased the observed benefit,
including the mammographic technique used (single view), the failure to achieve the intended
sample size and number of screenings, and the 70% compliance rate.
An updated USPSTF meta-analysis, which included results from the Age trial and longerterm results from the Gothenberg Breast Screening Trial,13 yielded results similar to those of
the earlier meta-analysis (relative risk for death from breast cancer, 0.85; 95% CI, 0.75 to
0.96); the number needed to invite for screening was 1904. A sensitivity analysis that
excluded a trial in which an outdated mammographic technique was used10 and a trial with
serious methodologic limitations11 did not substantially change the results.8 The decision to
change the USPSTF recommendation was heavily influenced by the nonsignificant findings
of the Age trial the only trial that specifically focused on women in their 40s. The lower
breast-cancer risk, lower mammographic sensitivity, and higher rate of false positive results
among younger women as compared with older women were considered to account for a
benefit-to-risk ratio that was inadequate to allow a recommendation of routine screening of
women under 50 years of age. However, this change in recommendation remains highly
controversial,22,23 especially because of the greater number of years of life expectancy
gained from preventing death from breast cancer in younger women. According to statistical
modeling,19 screening initiated at the age of 40 years rather than 50 years would avert one
additional death from breast cancer per 1000 women screened, resulting in 33 life-years
gained.
Frequency of Screening
A controversial change from the 2002 USPSTF guidelines to the 2009 guidelines was a
switch from recommending screening every 1 to 2 years to screening every 2 years.7,8
Supporting this change was the observation that reductions in mortality from breast cancer
were similar in the randomized trials that involved annual screening and those that involved
screening every 18 to 33 months.24 Moreover, there was little difference in the likelihood of
detecting advanced breast cancer with annual versus biennial screening programs. 25,26 In
statistical models,19 screening of women 50 to 69 years of age every 2 years maintained 81%
of the benefit associated with annual screening; as compared with screening every 2 years,
annual screening prevented about two additional deaths from breast cancer per 1000 women
screened.
In analyses based on data from the Surveillance, Epidemiology, and End Results (SEER)
program of the National Cancer Institute,27 a 2-year screening interval was not associated
with an increased risk of late-stage disease in women 50 years of age or older, as compared
with a 1-year screening interval, but it was associated with an increased risk in women 40 to
49 years of age (odds ratio, 1.35; 95% CI, 1.01 to 1.81) an observation attributed to the
faster growth rate of breast tumors in younger women. Although this observation would seem
to support annual screening for women in their 40s, a recent study showed that faster tumor
growth was only a minor contributor to the lower sensitivity of mammography in younger
women and that the major explanatory factor was poorer tumor detectability, predominantly
owing to greater breast density.28
Digital Mammography
The contrast between breast tumors and surrounding normal parenchyma is greater with
digital mammography than with film mammography, particularly when the breast tissue is
dense. In the Digital Mammographic Imaging Screening Trial (DMIST [ClinicalTrials.gov
number, NCT00008346])29 in which almost 50,000 asymptomatic women 40 years of age or
older underwent both digital and film mammography, the two techniques were equivalent
overall in sensitivity (70% and 66%, respectively) and specificity (92% for both). However,
in women under the age of 50 years, digital mammography was significantly more sensitive
than film (78% vs. 51%). Digital mammography offered a similar advantage for
premenopausal women and for women with dense breasts.
Risks and Costs of Screening

Aside from the discomfort many women experience from the breast compression necessary
for a technically optimal mammogram, mammography poses several risks, including rates of
false positive and false negative results, overdiagnosis, and radiation-induced cancers (Table
3Table 3
Risks Associated with Mammography.). Overdiagnosis, with consequent
overtreatment, is a particular concern. The diagnosis of ductal carcinoma in situ (DCIS) was
rare before the introduction of screening mammography and now accounts for approximately
25% of all cases of breast cancer, with more than 90% of DCIS cases detected only by
imaging.2 The natural history of DCIS is not clear, and many tumors, particularly those of
low grade, may not grow or become invasive,40 yet patients with DCIS are routinely treated
with lumpectomy and radiation therapy and often undergo mastectomy. On the basis of
simulation models, the incremental cost of screening every 2 years per quality-adjusted lifeyear from 40 to 80 years of age has been estimated to be between $35,000 and $47,000.41,42
Areas of Uncertainty
Risk Stratification
Since the probability that a woman will benefit from screening varies with her risk of breast
cancer, accurate risk stratification of individual patients is highly desirable. It is important to
identify the small group of women who are at high risk (i.e., their lifetime risk of breast
cancer exceeds 20 to 25%) and thus require earlier, more sensitive, and more frequent
screening than do women at lower risk. It is also important to identify the larger group of
women who are at moderately increased risk for breast cancer, as compared with the women
at average risk, particularly for women in their 40s for whom the risks and benefits of
screening may seem to be evenly balanced. This latter group may include women with a
lifetime risk of 15 to 20% or a 5-year risk above 1.66% (e.g., those with a first-degree relative
who had breast cancer before the age of 65 years or those with a previous breast-biopsy
specimen showing atypical hyperplasia or lobular carcinoma in situ). Since the risk of breast
cancer for a 40-year-old woman in one of these categories is at least as high as that for a 50year-old woman at average risk, screening mammography should be advised.43 Whether
more frequent screening or additional screening techniques would be beneficial is unknown
(as discussed below).
Mathematical models have been developed that integrate multiple risk factors to create a risk
score.44 Currently, the most commonly used risk-prediction model in the United States is the
National Cancer Institute's Breast Cancer Risk Assessment Tool (based on the Gail model).45
Validation studies have shown that it accurately predicts risk within a population but is much
less accurate in predicting risk for individual women46 and should not be used to determine
the need for screening with magnetic resonance imaging (MRI).9 The TyrerCuzick model47
includes additional variables that are not considered in the Gail model (e.g., cancer in seconddegree relatives), but its usefulness has not yet been validated.
Relevance and Generalizability of Data from Randomized Trials

Data obtained from randomized trials of screening mammography that were performed
decades ago may no longer be relevant. In light of subsequent improvements in technology, it
is possible that these earlier results underestimate the current benefit of screening, or they
may overestimate the current benefit because treatment options have improved. Furthermore,
since most of the participants in these earlier trials were white, the degree to which the results
are generalizable to other racial and ethnic groups is unclear. Young black women have a
higher incidence of breast cancer than white women,2 which might increase the benefit from
mammographic screening at the age of 40 years, but they also have a higher proportion of
high-grade breast cancers that are negative for estrogen and progesterone receptors and for
HER2 overexpression,48 which grow faster than other breast cancers and thus may be less
amenable to detection by screening. As compared with other racial and ethnic groups, Asian
women have a lower incidence of breast cancer2 and greater breast density,49 which might
attenuate the benefits of screening.
Value of Other Screening Methods

Since mammography is the only screening method to date that has been proved to reduce
mortality from breast cancer, any other type of screening must be carried out as a supplement
to mammography. Although clinical breast examination detects some cancers that are missed
on mammography, no randomized trial has compared the combination of mammography plus
clinical breast examination with mammography alone. Of three randomized trials designed to
compare clinical breast examination with no screening in countries without screeningmammography programs, one had inconclusive results50 and two are ongoing.51,52 Metaanalyses of randomized and nonrandomized studies of breast self-examination have shown
that it has no effect on mortality from breast cancer.53
Screening ultrasonography has been reported to result in up to a 30% absolute increase in the
detection of invasive cancer in women with dense breasts, for whom the sensitivity of
mammography is reduced and the risk of cancer is increased.54,55 However, the rate of false
positive results ranges from 2.4 to 12.9%, as compared with 0.7 to 6.0% for mammography.
Studies assessing the effect of screening ultrasonography on mortality from breast cancer are
under way in Japan and Sweden.
Although the use of MRI more than doubles diagnostic sensitivity when it is used to screen
women at high risk for breast cancer, it is not recommended for screening the general
population because of the higher rate of false positive results and higher cost.9
Breast tomosynthesis, a three-dimensional version of digital mammography that generates
images of thin sections of the breast, was recently approved for screening by the Food and
Drug Administration. However, this technique has not been shown to improve diagnostic
sensitivity, as compared with standard digital mammography.56
Guidelines
Although all medical professional organizations in industrialized countries recommend
screening mammography for women between 50 and 69 years of age, recommendations
differ substantially with respect to other age groups, screening intervals, and breast
examinations in the clinic or by the patient herself (Table 4Table 4

Guidelines for Breast-Cancer Screening.).
Conclusions and Recommendations

How should one approach the question of screening mammography in a patient in her 40s,
such as the woman described in the vignette? The decision should be individualized, with the
recognition that the probability of a benefit is greater for women at higher risk. This patient
has no major risk factors, such as a family history of breast cancer or a history of a
premalignant lesion on biopsy, that would put her at even moderately increased risk. Her
chance of having invasive breast cancer over the next 8 years is about 1 in 80, and her chance
of dying from it is about 1 in 400. Mammographic screening every 2 years will detect two out
of three cancers in women her age and will reduce her risk of death from breast cancer by
15%. However, there is about a 40% chance that she will be called back for further imaging
tests and a 3% chance that she will undergo biopsy, with a benign finding. Lifestyle
modifications (e.g., weight control and avoidance of excessive alcohol consumption) that
might lower her risk should also be discussed.
Given the data from randomized trials, which consistently show a 14 to 32% reduction in
mortality from breast cancer with annual or biennial mammography in women 50 to 69 years
of age, screening mammography should be recommended for women in this age group
provided that their life expectancy is 5 years or more. For women 70 years of age or older,
data from randomized trials are lacking, and the decision about screening should therefore be
individualized on the basis of life expectancy and the patient's preference.
On the basis of the DMIST study results,29 I would recommend digital mammography for
screening women in their 40s, older premenopausal women, and women of any age whose
breasts are heterogeneously dense or very dense.
Dr. Warner reports receiving grant support from Amersham Health, consulting fees from
Bayer Schering Pharma, and lecture fees from AstraZeneca.
Disclosure forms provided by the author are available with the full text of this article at
NEJM.org.
No other potential conflict of interest relevant to this article was reported.
An audio version of this article is available at NEJM.org.
Source Information
From the Division of Medical Oncology, Sunnybrook Health Sciences Centre, University of
Toronto, Toronto.
Address reprint requests to Dr. Warner at the Division of Medical Oncology, Sunnybrook
Health Sciences Centre, 2075 Bayview Ave., Toronto, ON M4N 3M5, Canada, or at
ellen.warner@sunnybrook.c
http://www.nejm.org/doi/full/10.1056/NEJMcp1101540
Breast cancer: prevention and control

Introduction
Breast cancer is the top cancer in women both in the developed and the developing world.
The incidence of breast cancer is increasing in the developing world due to increase life
expectancy, increase urbanization and adoption of western lifestyles. Although some risk
reduction might be achieved with prevention, these strategies cannot eliminate the majority of
breast cancers that develop in low- and middle-income countries where breast cancer is
diagnosed in very late stages. Therefore, early detection in order to improve breast cancer
outcome and survival remains the cornerstone of breast cancer control.
The recommended early detection strategies for low- and middle-income countries are
awareness of early signs and symptoms and screening by clinical breast examination in
demonstration areas. Mammography screening is very costly and is recommended for

countries with good health infrastructure that can afford a long-term programme.
Many low- and middle-income countries that face the double burden of cervical and breast
cancer need to implement combined cost-effective and affordable interventions to tackle
these highly preventable diseases.
WHO promotes breast cancer control within the context of national cancer control
programmes and integrated to noncommunicable disease prevention and control. WHO, with
the support of Komen Foundation, is at present conducting a 5-year breast cancer costeffectiveness study in 10 low- and middle-income countries. The project includes a
programme costing tool to assess affordability. It is expected that the results of this project
will contribute to provide evidence for shaping adequate breast cancer policies in less
developed countries.
Breast cancer burden

Breast cancer is the most common cancer in women worldwide, comprising 16% of all
female cancers. It is estimated that 519 000 women died in 2004 due to breast cancer, and
although breast cancer is thought to be a disease of the developed world, a majority (69%) of
all breast cancer deaths occurs in developing countries (WHO Global Burden of Disease,
2004).
Incidence rates vary greatly worldwide, with age standardized rates as high as 99.4 per 100
000 in North America. Eastern Europe, South America, Southern Africa, and western Asia
have moderate incidence rates, but these are increasing. The lowest incidence rates are found
in most African countries but here breast cancer incidence rates are also increasing.
Breast cancer survival rates vary greatly worldwide, ranging from 80% or over in North
America, Sweden and Japan to around 60% in middle-income countries and below 40% in
low-income countries (Coleman et al., 2008). The low survival rates in less developed
countries can be explained mainly by the lack of early detection programmes, resulting in a
high proportion of women presenting with late-stage disease, as well as by the lack of
adequate diagnosis and treatment facilities.
Breast cancer risk factors

Several risk factors for breast cancer have been well documented. However, for the majority
of women presenting with breast cancer it is not possible to identify specific risk factors
(IARC, 2008; Lacey et al., 2009).
A familial history of breast cancer increases the risk by a factor of two or three. Some
mutations, particularly in BRCA1, BRCA2 and p53 result in a very high risk for breast
cancer. However, these mutations are rare and account for a small portion of the total breast
cancer burden.
Reproductive factors associated with prolonged exposure to endogenous estrogens, such as
early menarche, late menopause, late age at first childbirth are among the most important risk
factors for breast cancer. Exogenous hormones also exert a higher risk for breast cancer. Oral
contraceptive and hormone replacement therapy users are at higher risk than non-users.
Breastfeeding has a protective effect (IARC, 2008, Lacey et al., 2009).
The contribution of various modifiable risk factors, excluding reproductive factors, to the
overall breast cancer burden has been calculated by Danaei et al. (Danaei et al., 2005). They
conclude that 21% of all breast cancer deaths worldwide are attributable to alcohol use,
overweight and obesity, and physical inactivity. This proportion was higher in high-income
countries (27%), and the most important contributor was overweight and obesity. In low- and
middle-income countries, the proportion of breast cancers attributable to these risk factors
was 18%, and physical inactivity was the most important determinant (10%).
The differences in breast cancer incidence between developed and developing countries can
partly be explained by dietary effects combined with later first childbirth, lower parity, and
shorter breastfeeding (Peto, 2001). The increasing adoption of western life-style in low- and
middle-income countries is an important determinant in the increase of breast cancer
incidence in these countries.
Breast cancer control

WHO promotes breast cancer control within the context of comprehensive national cancer
control programmes that are integrated to noncommunicable diseases and other related
problems. Comprehensive cancer control involves prevention, early detection, diagnosis and
treatment, rehabilitation and palliative care.
Raising general public awareness on the breast cancer problem and the mechanisms to
control as well as advocating for appropriate policies and programmes are key strategies of
population-based breast cancer control. Many low- and middle-income countries face now a
double burden of breast and cervical cancer which represent top cancer killers in women over
30 years old. These countries need to implement combined strategies that address both public
health problems in an effective and efficient way.
Prevention
Control of specific modifiable breast cancer risk factors as well as effective integrated
prevention of non-communicable diseases which promotes healthy diet, physical activity and
control of alcohol intake, overweight and obesity, could eventually have an impact in
reducing the incidence of breast cancer in the long term.
Early detection
Although some risk reduction might be achieved with prevention, these strategies cannot
eliminate the majority of breast cancers that develop in low- and middle-income countries.
Therefore, early detection in order to improve breast cancer outcome and survival remains the
cornerstone of breast cancer control (Anderson et al., 2008).
There are two early detection methods:
early diagnosis or awareness of early signs and symptoms in symptomatic

populations in order to facilitate diagnosis and early treatment, and
screening that is the systematic application of a screening test in a presumably

asymptomatic population. It aims to identify individuals with an abnormality
suggestive of cancer.
A screening programme is a far more complex undertaking that an early diagnosis

programme. (WHO, 2007).
Irrespective of the early detection method used, central to the success of population based
early detection are careful planning and a well organized and sustainable programme that
targets the right population group and ensures coordination, continuity and quality of actions
across the whole continuum of care. Targeting the wrong age group, such as, younger women
with low risk of breast cancer, could cause a lower number of breast cancers found per
woman screened and therefore reduce its cost-effectiveness. In addition, targeting younger
women would lead to more evaluation of benign tumours, which causes unnecessary
overload of health care facilities due to the use of addition diagnostic resources (Yip et al.,
2008).
Early diagnosis
Early diagnosis remains an important early detection strategy, particularly in low- and
middle-income countries where the diseases is diagnosed in late stages and resources are very
limited. There is some evidence that this strategy can produce "down staging" (increasing in
proportion of breast cancers detected at an early stage) of the disease to stages that are more
amenable to curative treatment (Yip et al., 2008).
Mammography screening
Mammography screening is the only screening method that has proven to be effective. It can
reduce breast cancer mortality by 20 to 30% in women over 50 yrs old in high-income
countries when the screening coverage is over 70% (IARC, 2008). Mammography screening
is very complex and resource intensive and no research of its effectiveness has been
conducted in low resource settings.
Breast self examination (BSE)

There is no evidence on the effect of screening through breast self-examination (BSE).
However, the practice of BSE has been seen to empower women, taking responsibility for
their own health. Therefore, BSE is recommend for raising awareness among women at risk
rather than as a screening method
References
Anderson BO et al. (2008). Guideline implementation for breast healthcare in low-income
and middle-income countries: overview of the Breast Health Global Initiative Global Summit
2007. Cancer, 113, 222143.
Coleman MP et al. (2008). Cancer survival in five continents: a worldwide population-based
study (CONCORD). Lancet Oncol, 9, 73056.
Danaei G et al. (2005). Causes of cancer in the world: comparative risk assessment of nine
behavioural and environmental risk factors. Lancet, 366, 178493.
IARC (2002). Breast cancer screening, IARC handbooks for cancer prevention, volume 7,
Lyon, International Agency for Research on Cancer, IARCpress.
IARC (2008). World cancer report 2008. Lyon, International Agency for Research on
Cancer.
Lacey JV Jr. et al. (2009). Breast cancer epidemiology according to recognized breast cancer
risk factors in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial
Cohort. BMC Cancer, 9, 84.
Peto J. (2001). Cancer epidemiology in the last century and the next decade. Nature, 411,
3905.
Yip CH et al. (2008). Guideline implementation for breast healthcare in low- and middleincome countries: early detection resource allocation. Cancer, 113, 224456.
WHO (2007). Cancer control: knowledge into action: WHO guide for effective programmes:
early detection.
WHO (2008). The global burden of disease: 2004 update.
http://www.who.int/cancer/detection/breastcancer/en/index3.html
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Articles
Breast cancer
Breast cancer
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of breast cancer.
Alternative Names
Mammograms; Mastectomy
Highlights
Breast Cancer Screening Guidelines
Experts continue to review new information on the timing and type of breast imaging studies
to best reduce the toll of breast cancer. At this point, recommendations vary, and each woman
should discuss options with her doctors to arrive at the plan that best matches her individual
needs and preferences.
Most guidelines recommend annual mammograms for women starting at age 40. The
U.S. Preventive Services Task Force recommends that women at average risk for
breast cancer have mammograms once every 2 years beginning at age 50.
Women at high risk for breast cancer because of BRCA mutations, family history, or
other factors, should have an MRI along with a mammogram every year.
FDA Withdraws Bevacizumab (Avastin)for Breast Cancer

In 2011, the Food and Drug Administration (FDA) revoked bevacizumabs (Avastin)
indication for treatment of metastatic breast cancer citing the drugs lack of effectiveness and
safety. Data indicate that bevacizumab does not significantly improve patients survival time
and that its risks outweigh its benefits. Bevacizumab remains approved for treating other
types of cancer.
Drug Approvals
Two new drugs were approved in 2012:
Pentuzumab (Perjeta) is the newest treatment for advanced HER2-positive breast

cancer.
Everolimus (Afinitor) is approved for advanced hormone receptor-positive, HER2negative breast cancer.
Introduction
Breast cancers are potentially life-threatening malignancies that develop in one or both
breasts. The structure of the female breast is important in understanding this cancer:
The interior of the female breast consists mostly of fatty and fibrous connective
tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain
small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the
milk through the breast and converge in a collecting chamber located just below the
nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of

origin) or invasive (spreading).
Female breasts are also known as mammary glands because they are able to produce milk.
Noninvasive Breast Cancer

Noninvasive breast cancers include:
Ductal carcinoma in situ (DCIS; also called intraductal carcinoma). DCIS consist of
cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left
untreated it may sometimes progress to an invasive, infiltrating ductal breast cancer.
DCIS is the most common type of noninvasive breast cancer.
Lobular carcinoma in situ (LCIS). Although it is technically not a cancer, lobular
carcinoma in situ is a marker for an increased risk of invasive breast cancer.
A diagnosis of these early cancers (DCIS and LCIS) is made when there is no evidence of
invasion.
Invasive Breast Cancer

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which
covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and
lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive
breast cancers include:
Invasive (also called infiltrating) ductal carcinoma. This type of invasive breast cancer
penetrates the wall of a milk-passage duct. It accounts for 70 - 80% of all breast
cancer cases.
Invasive (also called infiltrating) lobular carcinoma. This is invasive cancer that has
spread through the wall of a milk-producing lobule. It accounts for 10 - 15% of all
breast cancers. It may appear in both breasts, sometimes in several separate
locations.
Click the icon to see an image of the breast.
There are other less common breast cancers that are not discussed in this report.
Risk Factors
About 12% of women will develop invasive breast cancer in their lifetime. Each year in the
United States, about 230,000 women are diagnosed with invasive breast cancer. Although
breast cancer in men is rare, about 2,000 American men are diagnosed each year with
invasive breast cancer.
There are many different risk factors for breast cancer.
Age
Most cases of breast cancer occur in women older than age 60. According to the American
Cancer Society, about 1 in 8 cases of invasive breast cancer are found in women younger
than age 45, while 2 in 3 cases of invasive breast cancer occur in women age 55 and older.
Race and Ethnicity

Breast cancer is slightly more common among white woman than African-American, Asian,
Latina, or Native American women. However, African-American women tend to have more
aggressive types of breast cancer tumors and are more likely to die from breast cancer than
women of other races. It is unclear whether this is mainly due to biologic or socioeconomic
reasons. Social and economic factors make it less likely that African-American women will
be screened, so they are more likely to be diagnosed at a later stage. They are also less likely
to have access to effective treatments.
Breast cancer is also more prevalent among Jewish women of Eastern European (Ashkenazi)
descent (see Genetic Factors, below).
Family and Personal History

Women who have a family history of breast cancer are at increased risk for developing breast
cancer themselves. Having a first-degree relative (mother, sister, or daughter) who has been
diagnosed with breast cancer doubles the risk for developing breast cancer.
Women who have had ovarian cancer are at increased risk for developing breast cancer. And,
a personal history of breast cancer increases the risk of developing a new cancer in the same
or other breast.
Genetic Factors
About 5 - 10% of breast cancer cases are due to inherited genetic mutations.
BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for
most cases of hereditary breast cancers, ovarian cancers, or both in families with a history of
these cancers.
BRCA gene mutations are present in only about 0.5% of the overall population. However,
certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also
seen in some African-American and Hispanic women.
Screening Guidelines for BRCA Genes. The U.S. Preventive Services Task Force (USPSTF)
recommends that women at high risk should be tested for BRCA genes, but does not
recommend routine genetic counseling or testing in low-risk women (no family history of
BRCA 1 or 2 genetic mutations). Risk assessment is based on a womans family history of
breast and ovarian cancer (on both the maternal and paternal sides).
In general, a woman is considered at high risk for BRCA genes if she has a first-degree
relative (mother, daughter, or sister) or several second-degree relatives (grandmother, aunt)
diagnosed with breast or ovarian cancer. Women who do not have a family history of breast
cancer have a low probability of inheriting BRCA genes and do not need to be tested.
The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial.
Some studies have suggested that these mutations are linked to less lethal breast cancer.
Others suggest that they do not change prognosis or may worsen it. Women with these
genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1
mutations tend to develop tumors that are hormone receptor negative, which can behave more
aggressively.
Other Genetic Mutations. Other genes associated with increased hereditary breast cancer risk
include p53, CHEK2, ATM, and PTEN. Researchers are continuing to make progress in
discovering genetic variants of breast cancer. A recent study identified a subtype that appears
to share similarities with ovarian cancer and may benefit from similar treatments. The hope is
that these genetic analyses can lead to more targeted and precise drug treatments .
Exposure to Estrogen
Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman
is exposed to over her lifetime, the higher her risk for breast cancer.
Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at
menopause may slightly increase a womans risk for breast cancer.
Pregnancy. Women who have never had children or who had their first child after age 30
may have a slightly increased breast cancer risk. Having children at an early age, and having
multiple pregnancies, reduces breast cancer risk. Scientific evidence shows there is no
association between abortion and increased breast cancer risk.
Studies have been mixed on whether breastfeeding decreases breast cancer risk.
Breastfeeding reduces a woman's total number of menstrual cycles, and thereby estrogen
exposure, which may account for its possible protective effects. Some studies suggest that the
longer a woman breast-feeds, the lower her risk, and that breastfeeding may be most
protective for women with a family history of breast cancer.
Birth Control Pills. Although studies have been conflicting about whether estrogen in oral
contraceptives increase the chances for breast cancer, the most recent research indicates that
current or former oral contraceptive use does not significantly increase breast cancer risk.
Women who have used oral contraceptives may have slightly more risk for breast cancer than
women who have never used them, but this risk declines once a woman stops using birth
control pills.
Hormone Replacement Therapy. Hormone replacement therapy (HRT) uses either estrogen
alone (known as estrogen therapy [ET]) or estrogen in combination with progestogen (known
as EPT or combination hormone therapy):
Estrogen-progestogen therapy (EPT) is used by women who have a uterus, because

estrogen alone can increase the risk of uterine cancer. EPT significantly increases
the risk for developing and dying from breast cancer, especially when used for more
than 5 years.
Estrogen-only therapy (ET) is prescribed for women who have had a hysterectomy
and do not have a uterus. ET does not appear to increase the risk for breast cancer.
In fact, some studies indicate that ET may reduce breast cancer risk. However,
prolonged used of ET can increase the risk for other health problems including blood
clots, heart attack, stroke, and possibly ovarian cancer.
Hormone therapy (EPT or ET) should not be used by women at high risk for breast
cancer.
In general, most doctors recommend that women use HRT only for short-term (1 -2 years)
relief of menopausal symptoms. Current guidelines advise initiating hormone therapy around
the time of menopause only when women are in their 40s or 50s. Starting HRT past age 59
may increase the risk for breast cancer and other health problems.
Women who take HRT should be aware that they need regular mammogram screenings,
because HRT increases breast cancer density, making mammograms more difficult to read.
[For more information, see In-Depth Report #40: Menopause.]
Infertility and Infertility Treatments. Despite some concerns that infertility treatments using
the drug clomiphene may increase the risk for breast cancer, most studies do not show an
association. Some studies indicate that ovulation induction with clomiphene may actually
decrease breast cancer risk. (Clomphine is related to tamoxifen, a drug that is used for breast
cancer prevention in high-risk women.)
Breast Conditions
Certain breast conditions may increase the risk for breast cancer:
Dense breast tissue is associated with a higher risk for breast cancer. Studies
suggest that women with highly dense tissue have 2 - 6 times the risk of women with
the least dense tissue. Genetic factors play a large role in breast density. Hormone
replacement therapy also increases breast density. In addition, dense breasts make
mammograms more difficult to read, which increases the likelihood of missing early
signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical
hyperplasia, is a significant risk factor for breast cancer.
Some common benign breast abnormalities that pose very little or no risks for breast cancer
include:
Cysts. These mostly occur in women in their middle-to-late reproductive years and
can be eliminated simply by aspirating fluid from them.
Click the icon to see an image of cysts in the breast.
Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breastfeeding.
Click the icon to see an image of a breast abscess.
Nipple discharge. Discharge from the nipple is worrisome to patients, but it is unlikely
to be a sign of cancer. Unexplained discharge still warrants evaluation, however.
Click the icon to see an image of nipple discharge.
Mastalgia. This is breast pain that occurs in association with, or independently from,
the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast
pain associated with their menstrual cycle. In general, breast pain does not need
assessment unless it is severe and prolonged.
Physical Characteristics
The following physical characteristics have been associated with increased risk:
Obesity increases the risk for all types of estrogen receptor-positive breast cancers.
Women who gain weight after menopause are most at risk. (On a positive note,
losing weight after menopause decreases breast cancer risk.) In postmenopausal
women, estrogen is produced in fat tissue. High amounts of fatty tissue increase
levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense
bones are likely to have higher estrogen levels and to be at greater risk for breast
cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly
due to the higher estrogen levels associated with greater bone growth.
Environmental Factors
Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called
xenoestrogens, have been under suspicion for years. There has been particular concern with
pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and
pyrethroids (permethrin), but at this time evidence of any causal association is very weak.
Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent
miscarriage have a slightly increased risk for breast cancer. There may also be a slightly
increased risk for their daughters (commonly called "DES daughters"), who were exposed to
the drug when their mothers took it during pregnancy.
Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer.
Girls who receive high-dose radiation therapy for cancer face an increased risk for breast
cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for
women with BRCA genetic mutations. Women should avoid unnecessary and excessive
exposure to medical radiation, including x-rays and CT scans.
Lifestyle Factors
Alcohol consumption is a risk factor for breast cancer, especially for women have two or
more drinks a day.
Disproven Risk Factors

Antiperspirants or use of deodorants after shaving have not been linked with any higher risk
for breast cancer. There is also no evidence that bras increase breast risk. Abortion does not
increase risk.
Prevention and Lifestyle Factors

Exercise
Regular exercise, particularly vigorous exercise, appears to offer protection against breast
cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting
hormones such as estrogen. The American Cancer Society recommends engaging in 45 - 60
minutes of physical activity at least 5 days a week.
Exercise can also help women who have been diagnosed with breast cancer and may help
reduce the risk of breast cancer recurrence. Studies indicate that both aerobic and weight
training exercises benefit the body and the mind, and improve quality of life for breast cancer
survivors.
Physical activity contributes to health by reducing the heart rate, decreasing the risk for
cardiovascular disease, and reducing the amount of bone loss that is associated with age and
osteoporosis. Physical activity also helps the body use calories more efficiently, thereby
helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite,
and helps in the reduction of body fat.
Dietary Factors
Despite much research on the association between diet and breast cancer, there is still little
consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancer-
fighting" food. The American Cancer Societys dietary guidelines for cancer prevention
recommend that people:
Choose foods, serving sizes, and caloric contents that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for
breast cancer should consider not drinking alcohol at all).
For breast cancer survivors, the American Cancer Society recommends diets that include lots
of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy
products), moderation in soy foods, and moderate or no alcohol consumption.
Here are results from recent studies evaluating diet and breast cancer, for preventing both the
development of cancer and its recurrence:
Fats. Research is still mixed on the role that fats, and which specific types of fats,
play in breast cancer risk and prevention. According to results from the Womens
Health Initiative study of dietary fat and breast cancer, there is no definite evidence
that a low-fat diet will help prevent breast cancer. However, the study suggested that
women who normally eat a very high-fat diet may benefit by reducing their fat intake.
Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants,
which may help protect against the tissue damage linked to increased cancer risk.
Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene
and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best
sources for these nutrients. These fiber-rich foods are an essential part of a healthy
diet. However, it is not clear whether fruits and vegetables can specifically prevent
breast cancer development or recurrence.
Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as
yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal
women. Low-fat or non-fat dairy products are a healthier choice than high-fat
varieties.
Click the icon to see an image of vitamin D sources.
Soy. The American Cancer Society recommends that women with breast cancer eat
only moderate amounts of soy foods and avoid taking dietary supplements that
contain high amounts of isoflavones. Isoflavones are a type of phytoestrogen
(estrogen-like plant chemical). There have been concerns that high intakes of soy
may increase the risk of estrogen-responsive cancers such as breast cancer.
Click the icon to see an image of phytochemicals.
Specific Preventive Measures for High-Risk Women

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history,
should take as many preventive measures as possible, starting at an early age. The following
lifestyle choices may be beneficial:
Exercising and eating a healthy diet is the first essential rule.

High-risk premenopausal women might choose alternatives to oral contraceptives
and, if feasible, consider having children early in their life.
High-risk postmenopausal women should consider not taking hormone replacement

therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or
drinking very sparingly.
Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs)

act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others.
Two SERMs -- tamoxifen (Nolvadex, generic) and raloxifene (Evista) -- are approved for
breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not
recommended as prevention for women at low risk for breast cancer or its recurrence.
Women at high risk for breast cancer should discuss with their doctors the risks and benefits
of SERMs.
Preventive Surgery. Certain women who have a very high risk for breast cancer, due to
factors such as BRCA genetic mutations or strong family history of breast cancer, may
consider preventive (prophylactic) surgery. For these women, prophylactic mastectomy of
both breasts can reduce the risk of cancer by as much as 97%. Prophylactic bilateral salpingooophorectomy (removal of both ovaries and fallopian tubes) can halve the risk for breast
cancer and also significantly reduce the risk for ovarian cancer. Preventive surgery requires
careful and serious consideration, and you should be sure to seek a second opinion from an
oncologist before making a final decision.
Symptoms
Breast cancers in their early stages are usually painless. Often the first symptom is the
discovery of a hard lump. Half of such masses are found in the upper outer quarter of the
breast. The lump may make the affected breast appear elevated or asymmetric. The nipple
may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an
orange. In some cases there is a bloody or clear discharge from the nipple.
Many breast cancers, however, produce no symptoms and cannot be felt on examination.
With an increase in the use of mammogram screening programs during the last several
decades, more breast cancers are being discovered before there are any symptoms.
Diagnosis
Breast Examination by a Health Professional. Women ages 20 - 49 should have a physical
examination by a health professional every 1 - 2 years. Those over age 50 should be
examined annually.
Self-Examinations. Women are encouraged to perform self-examinations each month, but
some studies have reported no difference in mortality rates between women who do selfexamination and those who do not. This does not mean women should stop attempting selfexaminations, but they should not replace the annual examination done by a health
professional. Breast awareness may be as helpful as formal self exams as long as women who
notice a breast abnormality obtain a professional evaluation promptly.
Monthly Self-Examination
1. Pick a time of the month that is easy to remember and perform self-examination at that
time each month. The breast has normal patterns of thickness and lumpiness that change
within a monthly period, and a consistently scheduled examination will help differentiate
between what is normal from abnormal. Many doctors now recommend breast awareness
rather than formal monthly self-examinations.
2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly
larger than the other). Check for changes or redness in the nipple area. Look for changes in
the appearance of the skin. With hands on the hips, push the pelvis forward and pull the
shoulders back and observe the breasts for irregularities. Repeat the observation with hands
behind the head. Move each arm and shoulder forward.
3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over
the breast area. Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dimesized circles. Press lightly first to feel the breast area, then press harder using a circular
motion.
Using this motion, start from the collarbone and move downward to underneath the breast.
Shift the fingers slightly over, slightly overlapping the previously checked region, and work
upward back to the collarbone. Repeat this up-and-down examination until the entire breast
area has been examined. Be sure to cover the entire area from the collarbone to the bottom of
the breast area and from the middle of the chest to the armpits. Move the towel under the
other shoulder and repeat the procedure.
Examine the nipple area, by gently lifting and squeezing it and checking for discharge.
4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of
soap.)
Note: A lump can be any size or shape and can move around or remain fixed. Of special
concern are specific or unusual lumps that appear to be different from the normal varying
thicknesses in the breast.
Monthly breast self-exams should always include: visual inspection (with and without a
mirror) to note any changes in contour or texture, and manual inspection in standing and
reclining positions to note any unusual lumps or thicknesses.
Click the icon to see an image of a breast self-exam.
Mammograms
Current Recommendations for Screening. Mammography is a low-radiation screening
method for breast cancer. Mammograms can detect early breast cancers when they are most
curable. However, they can also raise alarm about cancer when it is not present (so-called
false-positive results). In addition, mammograms can lead to treatments that do not improve a
woman's outcome (so-called overdiagnosis). Experts disagree as to the relative benefits and
risks of routine screening mammography. Because of this, there is debate on when women
should begin to have mammograms and how frequently they should have them.
Most major professional groups, including The American Cancer Society and The American
College of Obstetrics and Gynecology recommend that women have a mammogram every
year starting at age 40.
The U.S. Preventive Services Task Force recommends:
For women ages 40 - 49 years, the USPSTF does not recommend routine screening
mammography. The decision to screen women in this age group should be made on
a case-by-case basis, taking the patient's values regarding specific benefits and
harms into account.
For women ages 50 - 74 years, the USPSTF recommends that screening
mammography be performed every other year.
Given the disagreement among experts, women, (particularly those in their 40s), should
discuss the risks and benefits of mammography with their doctors, and then base their
decisions on family history, general health, and personal values.
Mammograms in younger women produce a relatively high rate of false-positive results
(when the test falsely indicates breast cancer), and there is a risk of radiation exposure and
potentially unnecessary biopsies or surgeries. However, mammograms can help catch tumors
while they are in their earliest and most treatable stages. The most deadly types of breast
cancer tend to occur in women in their 40s.
To further complicate matters, not all early-stage breast cancers become life-threatening.
With current science, doctors cannot predict if an untreated early-stage tumor will progress to
a lethal stage. The issue of whether mammograms may contribute to overdiagnosis and
overtreatment is very controversial and is currently a hot topic of debate among breast cancer
researchers.
After a woman reaches age 50, her risk for developing breast cancer increases. (Women over
age 65 account for most new cases of breast cancer.) Women with risk factors for breast
cancer, including a close family member with the disease, should consider having annual
mammograms starting 10 years earlier than the age at which the relative was diagnosed.
Click the icon to see an image of a mammogram.
Other Imaging Techniques

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and
ultrasound techniques can detect very small tumors (less than half an inch). However, they
are expensive and time-consuming procedures, and ultrasound may yield more false-positive
results. Nevertheless, some doctors believe they are important in identifying small tumors
missed on mammography in women who are receiving lumpectomy or breast-conserving
surgeries. Such findings allow surgeons to remove the optimal amount of abnormal tissue.
Ultrasound may be particularly helpful for women with dense breast tissue who show signs of
breast cancer.
The American Cancer Society recommends that high-risk women have an MRI of their breast
performed with their annual mammogram, including those who have:
A BRCA1 or BRCA2 mutation
A first-degree relative (parent, sibling, or child) with a BRCA1 or BRCA2 mutation,

even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater based on
various risk assessment tools that evaluate family history and other factors
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome,

or may have one of these genetic syndromes based on a history in a first-degree
relative
For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for
detecting hidden tumors in the other breast. An important study reported that MRI scans of
women who were diagnosed with cancer in one breast detected over 90% of cancers in the
other breast that had been previously missed by mammography or clinical breast exam.
Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the
other breast. Some doctors advocate MRIs for all women newly diagnosed with breast
cancer; others oppose this view. MRI scans may be most useful for younger women with
breast cancer who have dense breast tissue that may obscure tumors from mammography
readings. MRIs are less likely to be helpful for older women with early tumors in one breast
and clear mammography readings in the other.
It is very important that women have MRIs at qualified centers that perform many of these
procedures each year. MRI is a complicated procedure and requires special equipment and
experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious
findings are detected.
Scintimammography. In scintimammography, a radioactive chemical is injected into the
circulatory system, which is then selectively taken up by the tumor and revealed on
mammograms. This method is used for women who have had abnormal mammograms or for
women who have dense breast tissue. It is not used for regular screening or as an alternative
to mammography.
Biopsy
A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic
examination of a tissue sample of the suspicious area).
When a lump can be felt and is suspicious for cancer on mammography, an

excisional biopsy may be recommended. This biopsy is a surgical procedure for
removing the suspicious tissue and typically requires general anesthesia.
Click the icon to see an image of breast biopsy.
A core biopsy involves a small incision and the insertion of a spring-loaded hollow
needle that removes several samples. The patient needs only a local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities,
but there is no lump. With this procedure, using mammography as a guide, the doctor
inserts a small wire hook through a hollow needle and into the suspicious tissue. The
needle is withdrawn, and the hook is used by the surgeon to locate and remove the
lesion. The patient may receive local or general anesthesia.
A vacuum-assisted device may be used for some biopsies. This uses a single probe
through which a vacuum is used to draw out tissue. It allows several samples to be
taken without having to remove and re-insert the probe.
Final analysis of the breast tissue may take several days.
Sentinel Node Biopsy

The sentinel lymph node is the first lymph node that cancer cells are likely to spread to from
the primary tumor (the original site of the cancer). Sentinel node biopsy is a procedure that
examines the sentinel node to determine if cancer has spread.
Click the icon to see an image of a sentinel node biopsy.
Sentinel node biopsy involves:
The procedure uses an injection of a tiny amount of a tracer, either a radioactivelylabeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node.
This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph
nodes will be cancer free, making further surgery unnecessary.
Patients who have a sentinel node biopsy tend to have better arm function and a shorter
hospital stay than those who have an axillary node biopsy. The American Society of Clinical
Oncology's guidelines recommend sentinel node biopsy instead of axillary lymph node
dissection for women with early stage breast cancer who do not have nodes that can be felt
during a physical exam.
Axillary Lymphadenectomy
If the sentinel node biopsy finds evidence that cancer has spread, the next diagnostic step is to
find out how far it has spread. To do this, the doctor performs a procedure called an axillary
lymphadenectomy, which partially or completely removes the lymph nodes in the armpit
beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2
days.
Click the icon to see an image of the axillary lymph nodes.
Once the lymph nodes are removed, they are analyzed to determine whether subsequent
treatment needs to be more or less aggressive:
If no cancer is found in the lymph nodes, the condition is referred to as node

negative breast cancer. The chances are good that the cancer has not spread and is
still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive.
Their presence increases the possibility that the cancer has spread microscopically
to other areas of the body.
In node-positive cases, it is still not known if the cancer has metastasized beyond the
lymph nodes or, if so, to what extent. The doctor may perform further tests to see if
the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain
(MRI or CT scan).
Side effects of the procedure may include increased risk for infection and pain, swelling in
the arm from fluid build-up, and impaired sensation and restricted movement in the affected
arm.
Prognosis
Breast cancer is the second most lethal cancer in women. (Lung cancer is the leading cancer
killer in women.) The good news is that early detection and new treatments have improved
survival rates. Unfortunately, women in lower social and economic groups still have
significantly lower survival rates than women in higher groups.
Several factors are used to determine the risk for recurrence and the likelihood of successful
treatment. They include:
Location of the tumor and how far it has spread

Whether the tumor is hormone receptor-positive or -negative
Tumor markers
Gene expression
Tumor size and shape
Rate of cell division
Women are now living longer with breast cancer. In the United States, there are currently
more than 2.6 million breast cancer survivors. Breast cancer death rates have declined
significantly in the past decade, especially for women younger than age 50. This decline may
be due to better screening and better treatment options. However, survivors face the
uncertainties of possible recurrent cancer and some risk for complications from the treatment
itself.
Recurrences of cancer usually develop within 5 years of treatment. About 25% of recurrences
and half of new cancers in the opposite breast occur after 5 years.
Location of the Tumor

The location of the tumor is a major factor in outlook:
If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes
(node negative), the 5-year survival rates with treatment are up to 99%.
If the cancer has spread to the lymph nodes or beyond the primary tumor site (node
positive), the 5-year survival rate is about 84%.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and
bone), the average 5-year survival rate is 23%. New drug therapies, particularly
aromatase inhibitors, have helped prolong survival for women with metastatic (stage
IV) cancer.
The location of the tumor within the breast is an important predictor. Tumors that develop
toward the outside of the breast tend to be less serious than those that occur more toward the
middle of the breast.
Hormone Receptor-Positive or -Negative

About two-thirds of breast cancer cells contain receptors, or binding sites, for the hormones
estrogen and progesterone.
Estrogen receptor-positive (ER-positive, or ER+) breast cancer means that estrogen

stimulates the growth of the cancer cells.
Progesterone receptor-positive (PR-positive, or PR+) means that progesterone
Breast cancer is considered hormone receptor-positive if the cells have receptors for
one or both of these hormones. About 75% of all breast cancers are estrogen
receptor-positive. Most breast cancers that are ER+ are also PR+.
Breast cancer is considered hormone receptor-negative if the cells lack these

receptors. About 25% of breast cancers are hormone receptor-negative.
Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to

hormone therapy such as tamoxifen or aromatase inhibitors. Hormone receptor-negative
tumors are referred to as "hormone insensitive" or "hormone resistant."
Women have a better prognosis if their tumors are hormone receptor-positive because these
cells grow more slowly than receptor-negative cells. In addition, women with hormone
receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors
can be treated only with chemotherapy.) Recent declines in breast cancer mortality rates have
been most significant among women with estrogen receptor-positive tumors, due in part to
the widespread use of post-surgical hormone-blocking therapy.
Tumor Markers
Tumor markers are proteins found in blood or urine when cancer is present. Although they
are not used to diagnose cancer, the presence of certain markers can help predict how
aggressive a patients cancer may be and how well the cancer may respond to certain types of
drugs.
Tumor markers relevant for breast cancer prognosis include:
HER2. The American Cancer Society recommends that all women newly diagnosed with
breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2positive cancer usually occurs in younger women and is more quickly-growing and
aggressive than other types of breast cancer. The HER2 marker is present in about 20% of
cases of invasive breast cancer. Two types of tests are used to detect HER2:
Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)
Either test may be used as long as it is performed by an accredited laboratory. Tests that are
not clearly positive or negative should be repeated.
Treatment with trastuzumab (Herceptin), lapatinib (Tykerb), or pentuzumab (Perjeta) may
help women who test positive for HER2. A genetic test can help determine which patients
with HER2-positive breast cancer may be good candidates for trastuzumab treatment.
Other Markers. Other markers that may be evaluated include CA 15-3, CA 27.29, CEA, ER,
PgR, uPA, and PAI-1.
Gene Expression Profiling

Gene expression profiling tests (Oncotype DX, MammaPrint) examine a set of genes in
tumor tissue to determine the likelihood of breast cancer recurrence. These tests are also used
to help determine whether adjuvant (following surgery) drug treatments should be given. The
American Society of Clinical Oncology and the National Comprehensive Cancer Network
recommend that gene expression profiling tests be administered to newly diagnosed patients
with node-negative, estrogen-receptor-positive breast cancer (only Oncotype DX is approved
for this use). Based on the results, a doctor can decide whether a patient who has had surgery
may benefit from chemotherapy.
Other Factors for Predicting Outlook

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated
tumors, which have indistinct margins, are more dangerous than those with well-defined
margins.
Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests
measure aspects of cancer cell division and may eventually prove to predict the disease. For
example, the mitotic index (MI) is a measurement of the rate at which cells divide. The
higher the MI, the more aggressive the cancer. Other tests measure cells at a certain phase of
their division.
Effect of Emotions and Psychological Support

Individual or group psychotherapy may be helpful for women with breast cancer who are
suffering emotionally. On a reassuring note, stress has been ruled out as a risk factor for
Treatment
The three main treatments of breast cancer are:
Surgery
Radiation
Drug therapy
No one treatment fits every patient, and combination therapy is usually required. The choice
is determined by many factors, including the age of the patient, menopausal status, the kind
of cancer (ductal verses lobular), its stage, and whether or not the tumor contains hormone
receptors.
Breast cancer treatments are defined as local or systemic:
Local Treatment. Surgery and radiation are considered local therapies because they
directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is
usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects
the whole body. Drugs may include either chemotherapy or hormone therapy. Drug
therapy may be used as primary therapy for patients for whom surgery or radiation
therapy is not appropriate, neoadjuvant therapy (before surgery or radiation) to shrink
tumors to a size that can be treated with local therapy, or as adjuvant therapy
(following surgery or radiation) to reduce the risk of cancer recurrence. For metastatic
cancer, drugs are used not to cure but to improve quality of life and prolong survival.
Any or all of these therapies may be used separately or, most often, in different combinations.
For example, radiation alone or with chemotherapy or hormone therapy may be beneficial
before surgery, if the tumor is large. Surgery followed by radiation and hormone therapy is
usually recommended for women with early-stage, hormone-sensitive cancer. There are
numerous clinical trials investigating new treatments and treatment combinations. Patients,
especially those with advanced stages of cancer, may wish to consider enrolling in a clinical
trial.
Cancer Stage and Treatment Options

Treatment strategies depend in part on the stage of the cancer.
Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (in situ"),
meaning that the cancer is still confined within breast ducts or lobules and has not yet spread
to surrounding tissues. Stage 0 cancer is classified as either:
Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that
have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast.
LCIS rarely develops into invasive breast cancer, but having it in one breast
increases the risk of developing cancer in the other breast.
Treatment options for DCIS include:
Breast-conserving surgery and radiation therapy (followed by hormone-blocking

therapy for women with hormone-sensitive cancer). Many doctors recommend this
approach.
Total mastectomy (followed by hormone-blocking therapy for women with hormonesensitive cancer)
Breast-conserving surgery without radiation therapy
Treatment options for LCIS include:
Regular exams and mammograms to monitor any potential changes (observation

treatment)
Hormone-blocking therapy to prevent development of breast cancer (for women with
hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely
recommended
Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond
the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.
Stage II cancer is classified as either stage IIA or stage IIb.
In stage IIA cancer the tumor is either:
No more than 2 centimeters and has spread to the underarm lymph nodes (axillary
lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes
In stage IIB cancer the tumor is either:
Larger than 2 centimeters and less than 5 centimeters and has spread to 1 - 3
axillary lymph nodes
Larger than 5 centimeters but has now spread to lymph nodes
Treatment options for stage I and stage II breast cancer may include:
Breast-conserving surgery (such as lumpectomy) followed by radiation therapy

Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes,

chemotherapy, or hormone-blocking therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for

women with HER2-positive cancer
Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories:
Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).
In stage IIIA breast cancer, the tumor is either of the following:
Not more than 5 centimeters and has spread to axillary lymph nodes
Larger than 5 centimeters and has spread to axillary nodes or to internal mammary
nodes.
Treatment options for stage IIIA breast cancer are the same as those for stages I and II.
In stage IIIB breast cancer, the tumor has spread to either of the following:
Tissues near the breast (including the skin or chest wall)

Lymph nodes within the breast or under the arm
Stage IIIB treatment options may include:
Chemotherapy, and possibly hormone therapy (sometimes in combination with

chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy)
with lymph node dissection followed by radiation therapy and possibly more
chemotherapy or hormone-blocking therapy
Clinical trials
Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:
10 or more of the underarm lymph nodes

Lymph nodes beneath the collarbone and near the neck on the same side of the
body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes
Treatment options for operable stage III breast cancer are the same as those for stage I and II
breast cancers.
In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the
collarbone and near the neck on the same side of the body as the affected breast. Treatment
options are the same as those for stage IIIB.
Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the
breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone.
The cancer at this stage is considered to be chronic and incurable, and the usefulness of
treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease
and slow its progression, as well as to reduce pain and discomfort.
Treatment options for stage IV cancer include:
Surgery or radiation for any localized tumors in the breast.

Chemotherapy, hormone-blocking therapy, or both. Targeted therapy with
trastuzumab (Herceptin), lapatinib (Tykerb), or pentuzumab (Perjeta) should be
considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate
drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as

high-dose chemotherapy with stem cell transplant.
Post-Treatment Care
The American Society of Clinical Oncology (ASCO) recommends follow-up care for patients
who have been treated for breast cancer:
Visit your doctor every 3 - 6 months for the first 3 years after your first cancer
treatment, every 6 - 12 months during the fourth and fifth year, and once a year
thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but
no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a

mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report
any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your
care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule
follow-up visits for re-evaluation of your treatment.
ASCO does not recommend the use of laboratory blood tests (complete blood counts,
carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDGPET scan, CT scan) for routine breast cancer follow-up.
Genetic counseling may be helpful if you have:
Ashkenazi Jewish heritage

Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast
cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed

with breast cancer
History of breast cancer in a male relative
Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how
long a woman should wait to become pregnant after breast cancer treatment. Because of the
connection between estrogen levels and breast cancer cell growth, some doctors recommend
delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer
recurrence and improve odds for survival. However, other studies indicate that conceiving 6
months after treatment does not negatively affect survival. Discuss with your doctor your risk
for recurrence, and when it may be safe to attempt pregnancy.
Recurrent Breast Cancer

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has
come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years
after treatment, but breast cancer can recur many years later. Treatment options are based on
the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and
the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent
cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.
Because most breast cancer recurrences are discovered by patients in between doctor visits, it
is important to notify your doctor if you experience any of the following symptoms. These
symptoms may be signs of breast cancer recurrence:
New lumps in the breast

Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge
Surgery
Surgery is a part of nearly every patient's treatment for breast cancer. The initial surgical
intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy
(the removal of the breast) was the standard treatment for nearly all breast cancers. Now,
many patients with early-stage cancers can choose breast-conserving treatment, or
lumpectomy followed by radiation, with or without chemotherapy.
For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined
with radiation therapy works as well as a modified radical mastectomy.
Breast-Conserving Procedures
Breast-conserving procedures are considered as appropriate and as successful as mastectomy
in most women with early stage breast cancer. All women should discuss these options fully
with their doctor. Recurrence rates with conservative surgery are highest in women under age
45. Some women choose mastectomy over breast-conserving treatment even if the latter is
appropriate because it gives them a greater sense of security and allows them to avoid
radiation therapy.
Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the
armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for
small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with
breast radiation therapy, to remove additional tissue (should the margins of the specimen
show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation
therapy is appropriate and as effective as mastectomy for most women with stage I or II
breast cancers.
Click the icon to see an illustrated series detailing breast lump removal surgery.
Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes

referred to as quadrantectomy) removes the cancer and a large area of breast tissue,
occasionally including some of the lining over the chest muscles. It is less invasive than a full
mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Studies
have found that breast-conserving surgeries plus postoperative radiotherapy offer the same
survival rates as radical mastectomy in most women with early breast cancer.
Mastectomy
Surgery to remove the breast (mastectomy) is important for women with operable breast
cancer who are not candidates for breast conserving surgeries. There are different variations
on the procedure:
A total mastectomy involves removal of the whole breast and sometimes lymph
nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes
under the arm, and some additional fat and skin. (A modified radical mastectomy
removes the entire breast and armpit lymph nodes, with the underlying chest wall
muscle.) For most patients, there are no survival advantages from radical
mastectomy compared to less invasive mastectomies.
Click the icon to see an illustrated series detailing mastectomy surgery.
Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area
of the procedure, and pain relievers may be necessary.
The most frequent complication of extensive lymph node removal is lymphedema, or
swelling, of the arm. The likelihood of edema can be lessened by removing only some of the
lymph nodes instead of all of them.
Infrequent complications include poor wound healing, bleeding, or a reaction to the

anesthesia.
After mastectomy and lymph node removal, women may experience numbness, tingling, and
difficulty in extending the arm fully. These effects can last for months or years afterward.
Breast Reconstruction
After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction,
which can be performed at the time of the mastectomy itself, if desired. Several studies have
indicated that women who take advantage of cosmetic surgery after breast cancer have a
better sense of well-being and a higher quality of life than women who do not choose
reconstructive surgery.
The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is
taken from elsewhere in the body. Muscle flap procedures are more complicated, however,
and blood transfusions may be required. If the nipple is removed, it is rebuilt from other body
tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast
that is identical to its partner, and additional operations may be necessary to achieve a
desirable effect.
Implants, including silicone implants, do not appear to put a woman at risk for breast cancer
recurrence. However, breast implants are not lifetime devices. About half of women who
receive an implant for breast reconstruction will need to have it removed or replaced about 10
years after implantation.
Click the icon to see an illustrated series detailing breast reconstruction surgery.
Radiation
Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor
in the breast or surrounding tissue. It is used for several weeks following lumpectomy or
partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce
the chance of breast cancer recurrence in the breast and chest wall. Radiation is also
important in advanced stages of cancer for relief of symptoms and to slow progression.
Research shows that radiation therapy is helpful for women of all ages, including those over
age 65.
Administration of Radiation Therapy

Radiation is generally administered in the following ways:
External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and
delivered externally by an x-ray machine that targets radiation to the whole breast. It may be
delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or
lymph node involvement). The treatment is generally given daily (except for weekends) for
about 6 weeks. Some hospitals offer a shortened course of 3 weeks of radiation for patients
with early-stage breast cancer.
Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy).
Implants are most often used as a radiation boost after whole breast radiation.
Side Effects of Radiation Therapy

Side effects of radiation include:
Fatigue is very common and increases with subsequent treatments, but most women
are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a
corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated
sessions, the skin may become moist and "weepy." Exposing the treated skin to air
as much as possible helps healing. Washing the affected skin with soap and water is
not harmful.
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.
Long-Term Complications
Future complications include:
Radiation to the left breast may increase the long-term risk for developing heart
disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in
younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft
tissue malignancies known as sarcomas.
Current advanced imaging techniques use precise radiation that reduces exposure. These
newer techniques are likely to reduce the risks for heart disease and other serious
complications.
Chemotherapy
Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by
injection. They work systemically by killing cancer cells throughout the body.
(Unfortunately, they also kill some normal cells, which accounts for many of their side
effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to
treat types of early-stage breast cancer.
Newer biologic drugs target specific proteins involved in cancer. Treatment with these drugs
is called targeted therapy. Because targeted therapy drugs do not work as systemically as
chemotherapy or hormone-blocking drugs, they tend to cause fewer widespread side effects,
although they also carry risks of their own
Chemotherapy needs to be tailored to the type of cancer involved. Women require different
treatments depending on whether the tumor is node-negative or -positive, hormone receptorpositive or -negative, or HER2-positive or -negative. Different treatment approaches are also
used for early-stage cancer and advanced cancer.
Adjuvant chemotherapy is administered following surgery and before radiation therapy.
Delaying chemotherapy until more than 12 weeks after surgery may increase the risk for
breast cancer recurrence and reduce the odds for survival.
Chemotherapy Drug Classes

Many different types of chemotherapy drugs are used to treat breast cancer. Common types
of chemotherapy drug classes include:
Anthracyclines include doxorubicin (Adriamycin, generic) and epirubicin (Ellence,

generic). Anthracycline-based combination regimens are often used to treat earlystage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol, generic) and docetaxel (Taxotere, generic). These
drugs may be particularly helpful for node-positive breast cancer. A newer
formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced
breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin, generic) and carboplatin
(Paraplatin, generic). These drugs may be used in combination regiments for
advanced cancer or for cancers associated with BRCA genes.
Chemotherapy Regimens for Early-Stage Breast Cancer

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug
classes rather than drug names. For example, regimens that contain an anthracycline drug
(such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as
docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and
methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy
regimens.
Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months.
Common chemotherapy regimens for early-stage breast cancer include:
AC (Doxorubicin and cyclophosphamide)

AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)
Chemotherapy for Advanced (Metastatic) Cancer

Patients who develop metastatic disease (cancer that spreads throughout the body) are
generally not curable. New advances in drug therapies, however, can help shrink tumors,
prolong survival, and improve quality of life.
Chemotherapy regimens for advanced cancer may use a single drug or a combination of
drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for
advanced breast cancer. Some specific individual drugs and combinations for advanced
cancer include:
Gemcitabine and paclitaxel. Gemcitabine (Gemzar, generic) is used in combination

with paclitaxel (Taxol, generic) as a first-line treatment option for women with
metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere, generic). Capecitabine is an oral
drug that is chemically related to 5-FU. In addition to combination treatment with
docetaxel, it is used in combination with a new type of drug, ixabepilone (Ixempra),
for patients with advanced breast cancer who have not responded to other types of
chemotherapy. It is also being studied in combination with other drugs.
Eribulin (Halaven) was approved in 2010 as a treatment for metastatic breast cancer
in patients who have already received at least two regimens of chemotherapy for
late-stage disease. The injectable drug is a synthetic compound of a chemical found
in a type of sea sponge.
Everolimus (Afinitor) was approved in 2012 for treatment of advanced hormone

receptor-positive, HER2-negative breast cancer.
Numerous chemotherapy drugs and drug combinations are being tested in clinical trials.
Patients with advanced breast cancer may also receive other types of drug treatments. For
example, bisphosphonate drugs such as zoledronic acid (Zometa) and pamidronate (Aredia,
generic), and the biologic drug denosumab (Xgeva), are important supportive drugs for
preventing fractures and reducing pain in people whose cancer has spread to the bones.
Targeted Therapy for Early-Stage HER2-Positive Breast Cancer

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody biologic drug that targets
the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage
breast cancer and are associated with more aggressive disease. Younger women tend to be
most affected.
Trastuzumab is given along with other chemotherapy drugs following lumpectomy or
mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and
death among women with early-stage breast cancer, but it increases the risk of heart
problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart
muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to
have regular heart monitoring, especially if they have already have heart problems.
Targeted Therapy for Advanced HER2-Positive Breast Cancer

Three targeted therapy (biologic) drugs are approved for the treatment of HER2-positive
advanced breast cancer:
Trastuzumab (Herceptin) is used after chemotherapy, along with drugs such as

paclitaxel.
Lapatinib (Tykerb) is used in combination with capecitabine (Xeloda). Research
suggests it may have fewer risks for heart problems than trastuzumab. Lapatinib is
also approved for combination use with letrozole (Femara, generic) as a first-line
treatment for hormone-positive and HER2-positive advanced breast cancer in
postmenopausal women for whom hormone treatment is recommended.
Pentuzumab (Perjeta) is used in combination with trastuzumab and docetaxel for
treatment of HER2 postive metastatic breast cancer. Pentuzumab is the newest type
of anti-HER2 therapy.
Side Effects of Chemotherapy

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses
and increase over the course of treatment.
Common side effects include:
Nausea and vomiting. Drugs such as ondansetron (Zofran, generic) and aprepitant
(Emend) can help relieve these side effects.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Serious short- and long-term complications can also occur and may vary depending on the
specific drugs used. They may include:
Anemia. Chemotherapy-induced anemia is usually treated with erythropoiesisstimulating drugs, which include epoietin alfa (Epogen, Procrit) and darberpetin alfa
(Aranesp). Doctors need to follow strict dosing guidelines when administering these
drugs. Patients should discuss the risks and benefits of erythropoiesis-stimulating
drugs with their oncologists. [For more information, see In-Depth Report #57:
Anemia.]
Increased chance for infection from severe reduction in white blood cells
(neutropenia). The addition of a drug called granulocyte colony-stimulating factor
(filgrastim and lenograstim) can help reduce the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause is a common side

effect of chemotherapy. A hormone medication called a gonadotropin-releasing
hormone analogue, which puts women in a temporary pre-pubescent state during
chemotherapy, may preserve fertility in some women. Women may also wish to
consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro
fertilization and freezing of embryos for later use. The American Society of Clinical
Oncology recommends that women being treated for cancer see a reproductive
specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
Some women report problems in concentration, motor function, and memory, which
can be long-term.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure,
particularly in women with pre-existing risk factors. Cumulative doses of
anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time
and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart
and central nervous system. Taxane therapy may also cause severe joint and muscle
pain in some patients.
Hormone Therapy
The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is
recommended for women whose breast cancers are hormone-receptor positive (either
estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread
to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for
patients with hormone receptor-positive ("hormone sensitive") tumors. Different types of
hormone therapy work in different ways by:
Blocking estrogen receptors in cancer cells (Tamoxifen)

Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)
Tamoxifen was the first widely used hormonal therapy drug, but today it is mainly used as
adjuvant therapy for premenopausal and perimenopausal women with hormone-sensitive
breast cancer. Postmenopausal women are now usually prescribed aromatase inhibitors.
Tamoxifen and Selective Estrogen Receptor Modulators (SERMs)

Tamoxifen (Nolvadex, generic) has been the standard hormonal drug used for breast cancer.
It belongs to a class of compounds called selective estrogen receptor modulators (SERMs).
SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in
place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth.
Because SERMs block estrogens effects on cancer cells, they are sometimes referred to as
"anti-estrogen" drugs.
Tamoxifen is used for all cancer stages in (mainly premenopausal) women with hormone
receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women.
Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer,
but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in
a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is
approved only for postmenopausal women with hormone-sensitive advanced breast cancer in
whom tamoxifen or aromatase inhibitors no longer work.
To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery
and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side
effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial)
cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a
symptom of uterine cancer. Tamoxifen risks for blood clots may be higher for obese women.
Tamoxifen interacts with certain types of antidepressants. In particular, the antidepressants
paroxetine (Paxil, generic) and fluoxetine (Prozac, generic) can weaken the effectiveness of
tamoxifen. Doctors recommend venlafaxine (Effexor, generic) as a first-line antidepressant
drug for women who take tamoxifen.
Less serious, but discomforting, side effects include hot flashes and mood swings. According
to one study, nearly 25% of women stop taking tamoxifen within 1 year because of these
symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years,
however, increases the risk for cancer recurrence and death. Talk with your doctor about
antidepressants or other therapies that may help you cope with tamoxifens side effects.
The American Society of Clinical Oncology (ASCO) current guidelines recommend that
postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen
therapy. Postmenopausal women who have already completed 5 years of tamoxifen therapy
can benefit from switching to an aromatase inhibitor for up to an additional 5 years to help
further reduce their risk of cancer recurrence. Several recent studies have indicated that
switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and
reduces the risk of death from breast cancer as well as other causes.
Aromatase Inhibitors
Aromatase inhibitors are recommended as first-line adjuvant therapy for postmenopausal
women with hormone-sensitive breast cancer. Aromatase inhibitors are taken for up to 5
years. They can be used either before or after tamoxifen treatment. (If women begin and then
discontinue aromatase inhibitors, they should consider switching to tamoxifen to complete
the 5-year treatment.)
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many
major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work
differently than tamoxifen. Tamoxifen interferes with tumors ability to use estrogen by
blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen
in the body.
Because these drugs cannot stop the ovaries of premenopausal women from producing
estrogen, they are recommended only for postmenopausal women.
There are currently three aromatase inhibitors approved for treating early-stage, hormone
receptor-positive breast cancer in postmenopausal women:
Anastrazole (Armidex, generic)

Exemestane (Aromasin, generic)
Letrozole (Femara, generic)
There are no significant differences between these three drugs. Women who cannot tolerate
one type of aromatase inhibitor can switch to a different one. All of these drugs are also
approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies
indicate that the introduction of aromatase inhibitors has helped greatly in prolonging
survival for women with advanced cancer.
Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine
cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone
loss and fractures. Women should have their bone mineral density monitored during
aromatase inhibitor treatment. In general, recent studies indicate that aromatase inhibitors are
better than tamoxifen in improving survival and reducing the risk of cancer recurrence.
Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.
Ovarian Ablation
Ovarian ablation is a treatment that stops estrogen production from the ovaries. Medications
can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also
shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but
several therapies are available to help prevent bone loss.)
Chemical Ovarian Ablation. Drug treatment to block ovarian production of estrogen is called
chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing
hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also
sometimes called GnRH agonists). These drugs block the release of the reproductive
hormones LH-RH, therefore stopping ovulation and estrogen production.
Bilateral Oophorectomy. Bilateral oophorectomy, the surgical removal of both ovaries, is a
surgical method of ovarian ablation. It may modestly improve breast cancer survival rates in
some premenopausal women whose tumors are hormone receptor-positive. In these women,
combining this procedure with tamoxifen may improve results beyond those of standard
chemotherapies. Oophorectomy does not benefit women after menopause, and its advantages
can be blunted in women who have received adjuvant chemotherapy. The procedure causes
sterility.
Resources
www.cancer.gov -- National Cancer Institute

www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.breastcancer.org -- BreastCancer.Org
www.komen.org -- Susan G. Komen Breast Cancer Foundation
www.nccn.org -- National Comprehensive Cancer Network
www.cancer.net -- Cancer.Net
www.cancer.gov/clinicaltrials -- Find clinical trials
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Version Info
Last Reviewed on 12/21/2012

Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard
Medical School; Physician, Massachusetts General Hospital. Also reviewed by David
Zieve, MD, MHA, Medical Director, A.D.A.M. Health Solutions, Ebix, Inc
Source: Breast cancer | University of Maryland Medical Center

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Breast Cancer Basics and You: Introduction

Past Issues / Spring - Summer 2010 Table of Contents
According to the National Cancer Institute (NCI), there were more than 194,000 new cases of
breast cancer in the United States in 2009. More than 40,000 people died of the disease. It
occurs in both men and women, although male breast cancer is rare.
The Breasts
Inside a woman's breast are 15 to 20 sections called lobes. Each lobe contains many smaller
sections called lobules. These are groups of tiny glands that make breast milk. Breast milk
flows through thin tubes called ducts to the nipple. Fat and other tissue fills the spaces
between the lobules and ducts. The breasts also contain lymph vessels, which are connected
to small, round masses of tissue called lymph nodes. Lymph nodes produce cells that help the
body fight infection. Groups of lymph nodes are near the breast in the underarm, above the
collarbone, and in the chest behind the breastbone.
The lobes and ducts of the breast, and nearby lymph nodes (above) are areas that cancer can
attack. The temporary inconvenience of a mammogram (opposite page) can save you from
troublesome and costly treatment and surgery by catching breast cancer early, when it is
easiest to treat.
Cancer Cells
Cancer begins in cells, the building blocks of body tissues. Cells grow and divide to form
new cells. When normal cells grow old or get damaged, they die, and new cells take their
place. Sometimes, new cells form when the body doesn't need them, and old or damaged cells
don't die as they should. The extra cells often form a mass of tissue called a lump, growth, or
tumor. Breast tumors can be benign (not cancer) or malignant (cancer).
Benign tumors:
are rarely a threat to life

can be removed and usually don't grow back
don't invade the tissues around them
don't spread to other parts of the body
Malignant tumors:
may be a threat to life

often can be removed but sometimes grow back
can invade and damage nearby organs and tissues (such as the chest wall)
can spread to other parts of the body
Breast cancer cells can break away from the original tumor and enter blood vessels or lymph
vessels, which branch into all the tissues of the body. The cancer cells may spread to lymph
nodes near the breast, or they may attach to other tissues, growing into new, damaging
tumors.
Risk Factors
No one knows what causes breast cancer. Risk factors for breast cancer include age, personal
and family health history, genetic changes, prior radiation therapy, reproductive and
menstrual history, race, breast density, overweight and obesity, physical inactivity, and
alcohol consumption. You can avoid some risk factors, such as drinking alcohol. Having a
risk factor does not mean that you will get breast cancer. Most women with risk factors never
develop breast cancer.
Symptoms
Early breast cancer usually doesn't cause symptoms. But as the tumor grows, it can change
how the breast looks or feels, including:
A lump or thickening in or near the breast or underarm area

A change in the size or shape of the breast
Dimpling or puckering in the skin of the breast. The skin may be ridged or pitted like
an orange.
A nipple turned inward into the breast
Fluid discharge from the nipple, especially if it's bloody
Scaly, red, or swollen skin on the breast, nipple, or areola (the dark area of skin at
the center of the breast)
See your healthcare provider about any of these symptoms that do not go away
Clinical Breast Exam

During a clinical breast exam, your healthcare provider inspects your breasts, underarms, and
collarbone area. She
looks for differences in size or shape between the breasts

checks your skin for a rash, dimpling, or other abnormal signs
may squeeze your nipples to check for fluid
uses the pads of her fingers to feel for lumps, pea-sized or larger
checks the lymph nodes near the breast to see if they are enlarged
If there is a lump, your healthcare provider will feel its size, shape, and texture. She will also
see if it moves easily. Lumps that are soft, smooth, round, and movable are likely to be
benign. Hard, oddly shaped ones that feel firmly attached within the breast are more likely to
be cancer, but you will need further tests to diagnose the problem.
Mammogram
Mammograms are x-ray pictures of breast tissue. They can often show a lump before it can
be felt. They also can reveal clusters of tiny specks of calcium. Lumps or specks can be from
cancer, precancerous cells, or other conditions. If you have a lump or calcium deposits, you
may need further tests to detect the presence of abnormal cells. You should get regular
screening mammograms to detect breast cancer early (see Screening for Breast Cancer, next
page).
Other Imaging Tests

Ultrasound devices use inaudible sound waves to create images that show whether a breast
lump is solid, filled with fluid (a cyst), or a mixture of both. Cysts usually are not cancer.
Solid lumps may be. Magnetic resonance imaging (MRI) devices detail the difference
between normal and diseased breast tissue.
Biopsy
Biopsies remove small amounts of breast tissue for inspection. They are the only sure way to
tell if you have cancer. A pathologist analyzes the tissue or fluid to determine the type of
cancer.
Testing Breast Tissue

Special tests on the diseased tissue may help determine treatment:
Hormone receptor tests: Some breast tumors need the hormones estrogen, progesterone, or
both, to grow. If they are found, your healthcare provider may recommend hormone therapy.
HER2/neu test: HER2/neu is a protein found on some types of cancer cells. This test shows
whether the tissue either has too much HER2/neu protein or too many copies of its gene. If
the breast tumor has too much HER2/neu, then targeted therapy, which uses drugs to block
the growth of breast cancer cells, may be an option.
Staging
The extent (stage) of breast cancer needs to be determined to help choose the best treatment.
The stage is based on the size of the cancer, whether it has invaded nearby tissues, or spread
to other parts of the body. Staging may involve blood and other tests.
Treatment
There are many options for treating breast cancer, including surgery, radiation therapy,
hormone treatment, chemotherapy, and targeted therapy. A person may receive more than
one type. What is best for one woman may not be best for another.
Local Therapy
Surgery and radiation are types of local therapy, used to remove or destroy cancer in the
breast.
Systemic Therapy
Hormone therapy, chemotherapy, and targeted therapy are types of systemic therapy. They
enter the bloodstream and destroy or control cancer throughout the body.
Your Choices
The treatment that's right for you depends mainly on the stage of the cancer, the results of the
hormone receptor tests, the result of the HER2/neu test, and your general health.
Clinical Trials
You may want to talk with your doctor about taking part in a clinical trial, a research study of
new treatment methods. Clinical trials are an important option at any stage of breast cancer.
If you are interested in a clinical trial, talk with your doctor. You may want to read the
National Cancer Institute (NCI) booklet Taking Part in Cancer Treatment Research Studies. It
describes how treatment studies are carried out and explains their possible benefits and risks
(for details see page 21).
The NCI Web site includes a section on clinical trials at http://www.cancer.gov/clinicaltrials.

It has general information about clinical trials, as well as detailed information about specific
ongoing studies of breast cancer. Information specialists at 1-800-4-CANCER () or at
LiveHelp at http://www.cancer.gov/help can answer questions and provide information about
clinical trials.
Side Effects
Your doctor can describe your treatment choices, the expected results, and possible side
effects. Because cancer therapy often damages healthy cells and tissues, side effects are
common. Before treatment, ask your healthcare team how to prevent or reduce them, and
how treatment may change your normal activities. Together, you and your healthcare team
can develop a treatment plan that meets your medical and personal needs.
Treatment Experts
Your doctor may refer you to a specialist, or you may ask for a referral. Specialists who treat
breast cancer include surgeons, medical oncologists, and radiation oncologists. You may be
referred to a plastic surgeon or reconstructive surgeon. Your healthcare team may also
include an oncology nurse and a registered dietitian.
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In-Depth Patient Education Reports
Articles
Breast cancer
Breast cancer
Description
An in-depth report on the causes, diagnosis, treatment, and prevention of breast cancer.
Alternative Names
Mammograms; Mastectomy
Highlights
Breast Cancer Screening Guidelines

Experts continue to review new information on the timing and type of breast imaging studies
to best reduce the toll of breast cancer. At this point, recommendations vary, and each woman
should discuss options with her doctors to arrive at the plan that best matches her individual
needs and preferences.
Most guidelines recommend annual mammograms for women starting at age 40. The
U.S. Preventive Services Task Force recommends that women at average risk for
breast cancer have mammograms once every 2 years beginning at age 50.
Women at high risk for breast cancer because of BRCA mutations, family history, or
other factors, should have an MRI along with a mammogram every year.
FDA Withdraws Bevacizumab (Avastin)for Breast Cancer

In 2011, the Food and Drug Administration (FDA) revoked bevacizumabs (Avastin)
indication for treatment of metastatic breast cancer citing the drugs lack of effectiveness and
safety. Data indicate that bevacizumab does not significantly improve patients survival time
and that its risks outweigh its benefits. Bevacizumab remains approved for treating other
types of cancer.
Drug Approvals
Two new drugs were approved in 2012:
Pentuzumab (Perjeta) is the newest treatment for advanced HER2-positive breast

cancer.
Everolimus (Afinitor) is approved for advanced hormone receptor-positive, HER2negative breast cancer.
Introduction
Breast cancers are potentially life-threatening malignancies that develop in one or both
breasts. The structure of the female breast is important in understanding this cancer:
The interior of the female breast consists mostly of fatty and fibrous connective
tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain
small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the
milk through the breast and converge in a collecting chamber located just below the
nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of

origin) or invasive (spreading).
Female breasts are also known as mammary glands because they are able to produce milk.
Noninvasive Breast Cancer

Noninvasive breast cancers include:
Ductal carcinoma in situ (DCIS; also called intraductal carcinoma). DCIS consist of
cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left
untreated it may sometimes progress to an invasive, infiltrating ductal breast cancer.
DCIS is the most common type of noninvasive breast cancer.
Lobular carcinoma in situ (LCIS). Although it is technically not a cancer, lobular
carcinoma in situ is a marker for an increased risk of invasive breast cancer.
A diagnosis of these early cancers (DCIS and LCIS) is made when there is no evidence of
invasion.
Invasive Breast Cancer

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which
covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and
lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive
breast cancers include:
Invasive (also called infiltrating) ductal carcinoma. This type of invasive breast cancer
penetrates the wall of a milk-passage duct. It accounts for 70 - 80% of all breast
cancer cases.
Invasive (also called infiltrating) lobular carcinoma. This is invasive cancer that has
spread through the wall of a milk-producing lobule. It accounts for 10 - 15% of all
breast cancers. It may appear in both breasts, sometimes in several separate
locations.
Click the icon to see an image of the breast.
There are other less common breast cancers that are not discussed in this report.
Risk Factors
About 12% of women will develop invasive breast cancer in their lifetime. Each year in the
United States, about 230,000 women are diagnosed with invasive breast cancer. Although
breast cancer in men is rare, about 2,000 American men are diagnosed each year with
invasive breast cancer.
There are many different risk factors for breast cancer.
Age
Most cases of breast cancer occur in women older than age 60. According to the American
Cancer Society, about 1 in 8 cases of invasive breast cancer are found in women younger
than age 45, while 2 in 3 cases of invasive breast cancer occur in women age 55 and older.
Race and Ethnicity

Breast cancer is slightly more common among white woman than African-American, Asian,
Latina, or Native American women. However, African-American women tend to have more
aggressive types of breast cancer tumors and are more likely to die from breast cancer than
women of other races. It is unclear whether this is mainly due to biologic or socioeconomic
reasons. Social and economic factors make it less likely that African-American women will
be screened, so they are more likely to be diagnosed at a later stage. They are also less likely
to have access to effective treatments.
Breast cancer is also more prevalent among Jewish women of Eastern European (Ashkenazi)
descent (see Genetic Factors, below).
Family and Personal History

Women who have a family history of breast cancer are at increased risk for developing breast
cancer themselves. Having a first-degree relative (mother, sister, or daughter) who has been
diagnosed with breast cancer doubles the risk for developing breast cancer.
Women who have had ovarian cancer are at increased risk for developing breast cancer. And,
a personal history of breast cancer increases the risk of developing a new cancer in the same
or other breast.
Genetic Factors
About 5 - 10% of breast cancer cases are due to inherited genetic mutations.
BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for
most cases of hereditary breast cancers, ovarian cancers, or both in families with a history of
these cancers.
BRCA gene mutations are present in only about 0.5% of the overall population. However,
certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also
seen in some African-American and Hispanic women.
Screening Guidelines for BRCA Genes. The U.S. Preventive Services Task Force (USPSTF)
recommends that women at high risk should be tested for BRCA genes, but does not
recommend routine genetic counseling or testing in low-risk women (no family history of
BRCA 1 or 2 genetic mutations). Risk assessment is based on a womans family history of
breast and ovarian cancer (on both the maternal and paternal sides).
In general, a woman is considered at high risk for BRCA genes if she has a first-degree
relative (mother, daughter, or sister) or several second-degree relatives (grandmother, aunt)
diagnosed with breast or ovarian cancer. Women who do not have a family history of breast
cancer have a low probability of inheriting BRCA genes and do not need to be tested.
The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial.
Some studies have suggested that these mutations are linked to less lethal breast cancer.
Others suggest that they do not change prognosis or may worsen it. Women with these
genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1
mutations tend to develop tumors that are hormone receptor negative, which can behave more
aggressively.
Other Genetic Mutations. Other genes associated with increased hereditary breast cancer risk
include p53, CHEK2, ATM, and PTEN. Researchers are continuing to make progress in
discovering genetic variants of breast cancer. A recent study identified a subtype that appears
to share similarities with ovarian cancer and may benefit from similar treatments. The hope is
that these genetic analyses can lead to more targeted and precise drug treatments .
Exposure to Estrogen
Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman
is exposed to over her lifetime, the higher her risk for breast cancer.
Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at
menopause may slightly increase a womans risk for breast cancer.
Pregnancy. Women who have never had children or who had their first child after age 30
may have a slightly increased breast cancer risk. Having children at an early age, and having
multiple pregnancies, reduces breast cancer risk. Scientific evidence shows there is no
association between abortion and increased breast cancer risk.
Studies have been mixed on whether breastfeeding decreases breast cancer risk.
Breastfeeding reduces a woman's total number of menstrual cycles, and thereby estrogen
exposure, which may account for its possible protective effects. Some studies suggest that the
longer a woman breast-feeds, the lower her risk, and that breastfeeding may be most
protective for women with a family history of breast cancer.
Birth Control Pills. Although studies have been conflicting about whether estrogen in oral
contraceptives increase the chances for breast cancer, the most recent research indicates that
current or former oral contraceptive use does not significantly increase breast cancer risk.
Women who have used oral contraceptives may have slightly more risk for breast cancer than
women who have never used them, but this risk declines once a woman stops using birth
control pills.
Hormone Replacement Therapy. Hormone replacement therapy (HRT) uses either estrogen
alone (known as estrogen therapy [ET]) or estrogen in combination with progestogen (known
as EPT or combination hormone therapy):
Estrogen-progestogen therapy (EPT) is used by women who have a uterus, because

estrogen alone can increase the risk of uterine cancer. EPT significantly increases
the risk for developing and dying from breast cancer, especially when used for more
than 5 years.
Estrogen-only therapy (ET) is prescribed for women who have had a hysterectomy
and do not have a uterus. ET does not appear to increase the risk for breast cancer.
In fact, some studies indicate that ET may reduce breast cancer risk. However,
prolonged used of ET can increase the risk for other health problems including blood
clots, heart attack, stroke, and possibly ovarian cancer.
Hormone therapy (EPT or ET) should not be used by women at high risk for breast
cancer.
In general, most doctors recommend that women use HRT only for short-term (1 -2 years)
relief of menopausal symptoms. Current guidelines advise initiating hormone therapy around
the time of menopause only when women are in their 40s or 50s. Starting HRT past age 59
may increase the risk for breast cancer and other health problems.
Women who take HRT should be aware that they need regular mammogram screenings,
because HRT increases breast cancer density, making mammograms more difficult to read.
[For more information, see In-Depth Report #40: Menopause.]
Infertility and Infertility Treatments. Despite some concerns that infertility treatments using
the drug clomiphene may increase the risk for breast cancer, most studies do not show an
association. Some studies indicate that ovulation induction with clomiphene may actually
decrease breast cancer risk. (Clomphine is related to tamoxifen, a drug that is used for breast
cancer prevention in high-risk women.)
Breast Conditions
Certain breast conditions may increase the risk for breast cancer:
Dense breast tissue is associated with a higher risk for breast cancer. Studies
suggest that women with highly dense tissue have 2 - 6 times the risk of women with
the least dense tissue. Genetic factors play a large role in breast density. Hormone
replacement therapy also increases breast density. In addition, dense breasts make
mammograms more difficult to read, which increases the likelihood of missing early
signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical
hyperplasia, is a significant risk factor for breast cancer.
Some common benign breast abnormalities that pose very little or no risks for breast cancer
include:
Cysts. These mostly occur in women in their middle-to-late reproductive years and
can be eliminated simply by aspirating fluid from them.
Click the icon to see an image of cysts in the breast.
Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breastfeeding.
Click the icon to see an image of a breast abscess.
Nipple discharge. Discharge from the nipple is worrisome to patients, but it is unlikely
to be a sign of cancer. Unexplained discharge still warrants evaluation, however.
Click the icon to see an image of nipple discharge.
Mastalgia. This is breast pain that occurs in association with, or independently from,
the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast
pain associated with their menstrual cycle. In general, breast pain does not need
assessment unless it is severe and prolonged.
Physical Characteristics
The following physical characteristics have been associated with increased risk:
Obesity increases the risk for all types of estrogen receptor-positive breast cancers.
Women who gain weight after menopause are most at risk. (On a positive note,
losing weight after menopause decreases breast cancer risk.) In postmenopausal
women, estrogen is produced in fat tissue. High amounts of fatty tissue increase
levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense
bones are likely to have higher estrogen levels and to be at greater risk for breast
cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly
due to the higher estrogen levels associated with greater bone growth.
Environmental Factors
Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called
xenoestrogens, have been under suspicion for years. There has been particular concern with
pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and
pyrethroids (permethrin), but at this time evidence of any causal association is very weak.
Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent
miscarriage have a slightly increased risk for breast cancer. There may also be a slightly
increased risk for their daughters (commonly called "DES daughters"), who were exposed to
the drug when their mothers took it during pregnancy.
Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer.
Girls who receive high-dose radiation therapy for cancer face an increased risk for breast
cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for
women with BRCA genetic mutations. Women should avoid unnecessary and excessive
exposure to medical radiation, including x-rays and CT scans.
Lifestyle Factors
Alcohol consumption is a risk factor for breast cancer, especially for women have two or
more drinks a day.
Disproven Risk Factors

Antiperspirants or use of deodorants after shaving have not been linked with any higher risk
for breast cancer. There is also no evidence that bras increase breast risk. Abortion does not
increase risk.
Prevention and Lifestyle Factors

Exercise
Regular exercise, particularly vigorous exercise, appears to offer protection against breast
cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting
hormones such as estrogen. The American Cancer Society recommends engaging in 45 - 60
minutes of physical activity at least 5 days a week.
Exercise can also help women who have been diagnosed with breast cancer and may help
reduce the risk of breast cancer recurrence. Studies indicate that both aerobic and weight
training exercises benefit the body and the mind, and improve quality of life for breast cancer
survivors.
Physical activity contributes to health by reducing the heart rate, decreasing the risk for
cardiovascular disease, and reducing the amount of bone loss that is associated with age and
osteoporosis. Physical activity also helps the body use calories more efficiently, thereby
helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite,
and helps in the reduction of body fat.
Dietary Factors
Despite much research on the association between diet and breast cancer, there is still little
consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancerfighting" food. The American Cancer Societys dietary guidelines for cancer prevention
recommend that people:
Choose foods, serving sizes, and caloric contents that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for
breast cancer should consider not drinking alcohol at all).
For breast cancer survivors, the American Cancer Society recommends diets that include lots
of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy
products), moderation in soy foods, and moderate or no alcohol consumption.
Here are results from recent studies evaluating diet and breast cancer, for preventing both the
development of cancer and its recurrence:
Fats. Research is still mixed on the role that fats, and which specific types of fats,
play in breast cancer risk and prevention. According to results from the Womens
Health Initiative study of dietary fat and breast cancer, there is no definite evidence
that a low-fat diet will help prevent breast cancer. However, the study suggested that
women who normally eat a very high-fat diet may benefit by reducing their fat intake.
Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants,
which may help protect against the tissue damage linked to increased cancer risk.
Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene
and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best
sources for these nutrients. These fiber-rich foods are an essential part of a healthy
diet. However, it is not clear whether fruits and vegetables can specifically prevent
Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as
yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal
women. Low-fat or non-fat dairy products are a healthier choice than high-fat
varieties.
Click the icon to see an image of vitamin D sources.
Soy. The American Cancer Society recommends that women with breast cancer eat
only moderate amounts of soy foods and avoid taking dietary supplements that
contain high amounts of isoflavones. Isoflavones are a type of phytoestrogen
(estrogen-like plant chemical). There have been concerns that high intakes of soy
may increase the risk of estrogen-responsive cancers such as breast cancer.
Click the icon to see an image of phytochemicals.
Specific Preventive Measures for High-Risk Women

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history,
should take as many preventive measures as possible, starting at an early age. The following
lifestyle choices may be beneficial:
Exercising and eating a healthy diet is the first essential rule.
High-risk premenopausal women might choose alternatives to oral contraceptives

and, if feasible, consider having children early in their life.
High-risk postmenopausal women should consider not taking hormone replacement

therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or
drinking very sparingly.
Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs)

act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others.
Two SERMs -- tamoxifen (Nolvadex, generic) and raloxifene (Evista) -- are approved for
breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not
recommended as prevention for women at low risk for breast cancer or its recurrence.
Women at high risk for breast cancer should discuss with their doctors the risks and benefits
of SERMs.
Preventive Surgery. Certain women who have a very high risk for breast cancer, due to
factors such as BRCA genetic mutations or strong family history of breast cancer, may
consider preventive (prophylactic) surgery. For these women, prophylactic mastectomy of
both breasts can reduce the risk of cancer by as much as 97%. Prophylactic bilateral salpingooophorectomy (removal of both ovaries and fallopian tubes) can halve the risk for breast
cancer and also significantly reduce the risk for ovarian cancer. Preventive surgery requires
careful and serious consideration, and you should be sure to seek a second opinion from an
oncologist before making a final decision.
Symptoms
Breast cancers in their early stages are usually painless. Often the first symptom is the
discovery of a hard lump. Half of such masses are found in the upper outer quarter of the
breast. The lump may make the affected breast appear elevated or asymmetric. The nipple
may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an
orange. In some cases there is a bloody or clear discharge from the nipple.
Many breast cancers, however, produce no symptoms and cannot be felt on examination.
With an increase in the use of mammogram screening programs during the last several
decades, more breast cancers are being discovered before there are any symptoms.
Diagnosis
Breast Examination by a Health Professional. Women ages 20 - 49 should have a physical
examination by a health professional every 1 - 2 years. Those over age 50 should be
examined annually.
Self-Examinations. Women are encouraged to perform self-examinations each month, but
some studies have reported no difference in mortality rates between women who do selfexamination and those who do not. This does not mean women should stop attempting selfexaminations, but they should not replace the annual examination done by a health
professional. Breast awareness may be as helpful as formal self exams as long as women who
notice a breast abnormality obtain a professional evaluation promptly.
Monthly Self-Examination
1. Pick a time of the month that is easy to remember and perform self-examination at that
time each month. The breast has normal patterns of thickness and lumpiness that change
within a monthly period, and a consistently scheduled examination will help differentiate
between what is normal from abnormal. Many doctors now recommend breast awareness
rather than formal monthly self-examinations.
2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly
larger than the other). Check for changes or redness in the nipple area. Look for changes in
the appearance of the skin. With hands on the hips, push the pelvis forward and pull the
shoulders back and observe the breasts for irregularities. Repeat the observation with hands
behind the head. Move each arm and shoulder forward.
3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over
the breast area. Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dimesized circles. Press lightly first to feel the breast area, then press harder using a circular
motion.
Using this motion, start from the collarbone and move downward to underneath the breast.
Shift the fingers slightly over, slightly overlapping the previously checked region, and work
upward back to the collarbone. Repeat this up-and-down examination until the entire breast
area has been examined. Be sure to cover the entire area from the collarbone to the bottom of
the breast area and from the middle of the chest to the armpits. Move the towel under the
other shoulder and repeat the procedure.
Examine the nipple area, by gently lifting and squeezing it and checking for discharge.
4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of
soap.)
Note: A lump can be any size or shape and can move around or remain fixed. Of special
concern are specific or unusual lumps that appear to be different from the normal varying
thicknesses in the breast.
Monthly breast self-exams should always include: visual inspection (with and without a
mirror) to note any changes in contour or texture, and manual inspection in standing and
reclining positions to note any unusual lumps or thicknesses.
Click the icon to see an image of a breast self-exam.
Mammograms
Current Recommendations for Screening. Mammography is a low-radiation screening
method for breast cancer. Mammograms can detect early breast cancers when they are most
curable. However, they can also raise alarm about cancer when it is not present (so-called
false-positive results). In addition, mammograms can lead to treatments that do not improve a
woman's outcome (so-called overdiagnosis). Experts disagree as to the relative benefits and
risks of routine screening mammography. Because of this, there is debate on when women
should begin to have mammograms and how frequently they should have them.
Most major professional groups, including The American Cancer Society and The American
College of Obstetrics and Gynecology recommend that women have a mammogram every
year starting at age 40.
The U.S. Preventive Services Task Force recommends:
For women ages 40 - 49 years, the USPSTF does not recommend routine screening
mammography. The decision to screen women in this age group should be made on
a case-by-case basis, taking the patient's values regarding specific benefits and
harms into account.
For women ages 50 - 74 years, the USPSTF recommends that screening

mammography be performed every other year.
Given the disagreement among experts, women, (particularly those in their 40s), should
discuss the risks and benefits of mammography with their doctors, and then base their
decisions on family history, general health, and personal values.
Mammograms in younger women produce a relatively high rate of false-positive results
(when the test falsely indicates breast cancer), and there is a risk of radiation exposure and
potentially unnecessary biopsies or surgeries. However, mammograms can help catch tumors
while they are in their earliest and most treatable stages. The most deadly types of breast
cancer tend to occur in women in their 40s.
To further complicate matters, not all early-stage breast cancers become life-threatening.
With current science, doctors cannot predict if an untreated early-stage tumor will progress to
a lethal stage. The issue of whether mammograms may contribute to overdiagnosis and
overtreatment is very controversial and is currently a hot topic of debate among breast cancer
researchers.
After a woman reaches age 50, her risk for developing breast cancer increases. (Women over
age 65 account for most new cases of breast cancer.) Women with risk factors for breast
cancer, including a close family member with the disease, should consider having annual
mammograms starting 10 years earlier than the age at which the relative was diagnosed.
Click the icon to see an image of a mammogram.
Other Imaging Techniques

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and
ultrasound techniques can detect very small tumors (less than half an inch). However, they
are expensive and time-consuming procedures, and ultrasound may yield more false-positive
results. Nevertheless, some doctors believe they are important in identifying small tumors
missed on mammography in women who are receiving lumpectomy or breast-conserving
surgeries. Such findings allow surgeons to remove the optimal amount of abnormal tissue.
Ultrasound may be particularly helpful for women with dense breast tissue who show signs of
breast cancer.
The American Cancer Society recommends that high-risk women have an MRI of their breast
performed with their annual mammogram, including those who have:
A BRCA1 or BRCA2 mutation

A first-degree relative (parent, sibling, or child) with a BRCA1 or BRCA2 mutation,
even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater based on
various risk assessment tools that evaluate family history and other factors
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome,

or may have one of these genetic syndromes based on a history in a first-degree
relative
For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for
detecting hidden tumors in the other breast. An important study reported that MRI scans of
women who were diagnosed with cancer in one breast detected over 90% of cancers in the
other breast that had been previously missed by mammography or clinical breast exam.
Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the
other breast. Some doctors advocate MRIs for all women newly diagnosed with breast
cancer; others oppose this view. MRI scans may be most useful for younger women with
breast cancer who have dense breast tissue that may obscure tumors from mammography
readings. MRIs are less likely to be helpful for older women with early tumors in one breast
and clear mammography readings in the other.
It is very important that women have MRIs at qualified centers that perform many of these
procedures each year. MRI is a complicated procedure and requires special equipment and
experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious
findings are detected.
Scintimammography. In scintimammography, a radioactive chemical is injected into the
circulatory system, which is then selectively taken up by the tumor and revealed on
mammograms. This method is used for women who have had abnormal mammograms or for
women who have dense breast tissue. It is not used for regular screening or as an alternative
to mammography.
Biopsy
A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic
examination of a tissue sample of the suspicious area).
When a lump can be felt and is suspicious for cancer on mammography, an

excisional biopsy may be recommended. This biopsy is a surgical procedure for
removing the suspicious tissue and typically requires general anesthesia.
Click the icon to see an image of breast biopsy.
A core biopsy involves a small incision and the insertion of a spring-loaded hollow
needle that removes several samples. The patient needs only a local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities,
but there is no lump. With this procedure, using mammography as a guide, the doctor
inserts a small wire hook through a hollow needle and into the suspicious tissue. The
needle is withdrawn, and the hook is used by the surgeon to locate and remove the
lesion. The patient may receive local or general anesthesia.
A vacuum-assisted device may be used for some biopsies. This uses a single probe
through which a vacuum is used to draw out tissue. It allows several samples to be
taken without having to remove and re-insert the probe.
Final analysis of the breast tissue may take several days.
Sentinel Node Biopsy

The sentinel lymph node is the first lymph node that cancer cells are likely to spread to from
the primary tumor (the original site of the cancer). Sentinel node biopsy is a procedure that
examines the sentinel node to determine if cancer has spread.
Click the icon to see an image of a sentinel node biopsy.
Sentinel node biopsy involves:
The procedure uses an injection of a tiny amount of a tracer, either a radioactivelylabeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node.
This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph
nodes will be cancer free, making further surgery unnecessary.
Patients who have a sentinel node biopsy tend to have better arm function and a shorter
hospital stay than those who have an axillary node biopsy. The American Society of Clinical
Oncology's guidelines recommend sentinel node biopsy instead of axillary lymph node
dissection for women with early stage breast cancer who do not have nodes that can be felt
during a physical exam.
Axillary Lymphadenectomy
If the sentinel node biopsy finds evidence that cancer has spread, the next diagnostic step is to
find out how far it has spread. To do this, the doctor performs a procedure called an axillary
lymphadenectomy, which partially or completely removes the lymph nodes in the armpit
beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2
days.
Click the icon to see an image of the axillary lymph nodes.
Once the lymph nodes are removed, they are analyzed to determine whether subsequent
treatment needs to be more or less aggressive:
If no cancer is found in the lymph nodes, the condition is referred to as node

negative breast cancer. The chances are good that the cancer has not spread and is
still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive.
Their presence increases the possibility that the cancer has spread microscopically
to other areas of the body.
In node-positive cases, it is still not known if the cancer has metastasized beyond the
lymph nodes or, if so, to what extent. The doctor may perform further tests to see if
the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain
(MRI or CT scan).
Side effects of the procedure may include increased risk for infection and pain, swelling in
the arm from fluid build-up, and impaired sensation and restricted movement in the affected
arm.
Prognosis
Breast cancer is the second most lethal cancer in women. (Lung cancer is the leading cancer
killer in women.) The good news is that early detection and new treatments have improved
survival rates. Unfortunately, women in lower social and economic groups still have
significantly lower survival rates than women in higher groups.
Several factors are used to determine the risk for recurrence and the likelihood of successful
treatment. They include:
Location of the tumor and how far it has spread

Whether the tumor is hormone receptor-positive or -negative
Tumor markers
Gene expression
Tumor size and shape
Rate of cell division
Women are now living longer with breast cancer. In the United States, there are currently
more than 2.6 million breast cancer survivors. Breast cancer death rates have declined
significantly in the past decade, especially for women younger than age 50. This decline may
be due to better screening and better treatment options. However, survivors face the
uncertainties of possible recurrent cancer and some risk for complications from the treatment
itself.
Recurrences of cancer usually develop within 5 years of treatment. About 25% of recurrences
and half of new cancers in the opposite breast occur after 5 years.
Location of the Tumor

The location of the tumor is a major factor in outlook:
If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes
(node negative), the 5-year survival rates with treatment are up to 99%.
If the cancer has spread to the lymph nodes or beyond the primary tumor site (node
positive), the 5-year survival rate is about 84%.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and
bone), the average 5-year survival rate is 23%. New drug therapies, particularly
aromatase inhibitors, have helped prolong survival for women with metastatic (stage
IV) cancer.
The location of the tumor within the breast is an important predictor. Tumors that develop
toward the outside of the breast tend to be less serious than those that occur more toward the
middle of the breast.
Hormone Receptor-Positive or -Negative

About two-thirds of breast cancer cells contain receptors, or binding sites, for the hormones
estrogen and progesterone.
Estrogen receptor-positive (ER-positive, or ER+) breast cancer means that estrogen

Progesterone receptor-positive (PR-positive, or PR+) means that progesterone
Breast cancer is considered hormone receptor-positive if the cells have receptors for
one or both of these hormones. About 75% of all breast cancers are estrogen
receptor-positive. Most breast cancers that are ER+ are also PR+.
Breast cancer is considered hormone receptor-negative if the cells lack these

receptors. About 25% of breast cancers are hormone receptor-negative.
Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to

hormone therapy such as tamoxifen or aromatase inhibitors. Hormone receptor-negative
tumors are referred to as "hormone insensitive" or "hormone resistant."
Women have a better prognosis if their tumors are hormone receptor-positive because these
cells grow more slowly than receptor-negative cells. In addition, women with hormone
receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors
can be treated only with chemotherapy.) Recent declines in breast cancer mortality rates have
been most significant among women with estrogen receptor-positive tumors, due in part to
the widespread use of post-surgical hormone-blocking therapy.
Tumor Markers
Tumor markers are proteins found in blood or urine when cancer is present. Although they
are not used to diagnose cancer, the presence of certain markers can help predict how
aggressive a patients cancer may be and how well the cancer may respond to certain types of
drugs.
Tumor markers relevant for breast cancer prognosis include:
HER2. The American Cancer Society recommends that all women newly diagnosed with
breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2positive cancer usually occurs in younger women and is more quickly-growing and
aggressive than other types of breast cancer. The HER2 marker is present in about 20% of
cases of invasive breast cancer. Two types of tests are used to detect HER2:
Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)
Either test may be used as long as it is performed by an accredited laboratory. Tests that are
not clearly positive or negative should be repeated.
Treatment with trastuzumab (Herceptin), lapatinib (Tykerb), or pentuzumab (Perjeta) may
help women who test positive for HER2. A genetic test can help determine which patients
with HER2-positive breast cancer may be good candidates for trastuzumab treatment.
Other Markers. Other markers that may be evaluated include CA 15-3, CA 27.29, CEA, ER,
PgR, uPA, and PAI-1.
Gene Expression Profiling

Gene expression profiling tests (Oncotype DX, MammaPrint) examine a set of genes in
tumor tissue to determine the likelihood of breast cancer recurrence. These tests are also used
to help determine whether adjuvant (following surgery) drug treatments should be given. The
American Society of Clinical Oncology and the National Comprehensive Cancer Network
recommend that gene expression profiling tests be administered to newly diagnosed patients
with node-negative, estrogen-receptor-positive breast cancer (only Oncotype DX is approved
for this use). Based on the results, a doctor can decide whether a patient who has had surgery
may benefit from chemotherapy.
Other Factors for Predicting Outlook

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated
tumors, which have indistinct margins, are more dangerous than those with well-defined
margins.
Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests
measure aspects of cancer cell division and may eventually prove to predict the disease. For
example, the mitotic index (MI) is a measurement of the rate at which cells divide. The
higher the MI, the more aggressive the cancer. Other tests measure cells at a certain phase of
their division.
Effect of Emotions and Psychological Support

Individual or group psychotherapy may be helpful for women with breast cancer who are
suffering emotionally. On a reassuring note, stress has been ruled out as a risk factor for
Treatment
The three main treatments of breast cancer are:
Surgery
Radiation
Drug therapy
No one treatment fits every patient, and combination therapy is usually required. The choice
is determined by many factors, including the age of the patient, menopausal status, the kind
of cancer (ductal verses lobular), its stage, and whether or not the tumor contains hormone
receptors.
Breast cancer treatments are defined as local or systemic:
Local Treatment. Surgery and radiation are considered local therapies because they
directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is
usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects
the whole body. Drugs may include either chemotherapy or hormone therapy. Drug
therapy may be used as primary therapy for patients for whom surgery or radiation
therapy is not appropriate, neoadjuvant therapy (before surgery or radiation) to shrink
tumors to a size that can be treated with local therapy, or as adjuvant therapy
(following surgery or radiation) to reduce the risk of cancer recurrence. For metastatic
cancer, drugs are used not to cure but to improve quality of life and prolong survival.
Any or all of these therapies may be used separately or, most often, in different combinations.
For example, radiation alone or with chemotherapy or hormone therapy may be beneficial
before surgery, if the tumor is large. Surgery followed by radiation and hormone therapy is
usually recommended for women with early-stage, hormone-sensitive cancer. There are
numerous clinical trials investigating new treatments and treatment combinations. Patients,
especially those with advanced stages of cancer, may wish to consider enrolling in a clinical
trial.
Cancer Stage and Treatment Options

Treatment strategies depend in part on the stage of the cancer.
Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (in situ"),
meaning that the cancer is still confined within breast ducts or lobules and has not yet spread
to surrounding tissues. Stage 0 cancer is classified as either:
Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that
have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast.
LCIS rarely develops into invasive breast cancer, but having it in one breast
increases the risk of developing cancer in the other breast.
Treatment options for DCIS include:
Breast-conserving surgery and radiation therapy (followed by hormone-blocking

therapy for women with hormone-sensitive cancer). Many doctors recommend this
approach.
Total mastectomy (followed by hormone-blocking therapy for women with hormonesensitive cancer)
Breast-conserving surgery without radiation therapy
Treatment options for LCIS include:
Regular exams and mammograms to monitor any potential changes (observation

treatment)
Hormone-blocking therapy to prevent development of breast cancer (for women with
hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely
recommended
Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond
the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.
Stage II cancer is classified as either stage IIA or stage IIb.
In stage IIA cancer the tumor is either:
No more than 2 centimeters and has spread to the underarm lymph nodes (axillary
lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes
In stage IIB cancer the tumor is either:
Larger than 2 centimeters and less than 5 centimeters and has spread to 1 - 3
axillary lymph nodes
Larger than 5 centimeters but has now spread to lymph nodes
Treatment options for stage I and stage II breast cancer may include:
Breast-conserving surgery (such as lumpectomy) followed by radiation therapy

Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes,

chemotherapy, or hormone-blocking therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for

women with HER2-positive cancer
Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories:
Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).
In stage IIIA breast cancer, the tumor is either of the following:
Not more than 5 centimeters and has spread to axillary lymph nodes
Larger than 5 centimeters and has spread to axillary nodes or to internal mammary
nodes.
Treatment options for stage IIIA breast cancer are the same as those for stages I and II.
In stage IIIB breast cancer, the tumor has spread to either of the following:
Tissues near the breast (including the skin or chest wall)

Lymph nodes within the breast or under the arm
Stage IIIB treatment options may include:
Chemotherapy, and possibly hormone therapy (sometimes in combination with

chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy)
with lymph node dissection followed by radiation therapy and possibly more
chemotherapy or hormone-blocking therapy
Clinical trials
Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:
10 or more of the underarm lymph nodes

Lymph nodes beneath the collarbone and near the neck on the same side of the
body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes
Treatment options for operable stage III breast cancer are the same as those for stage I and II
breast cancers.
In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the
collarbone and near the neck on the same side of the body as the affected breast. Treatment
options are the same as those for stage IIIB.
Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the
breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone.
The cancer at this stage is considered to be chronic and incurable, and the usefulness of
treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease
and slow its progression, as well as to reduce pain and discomfort.
Treatment options for stage IV cancer include:
Surgery or radiation for any localized tumors in the breast.

Chemotherapy, hormone-blocking therapy, or both. Targeted therapy with
trastuzumab (Herceptin), lapatinib (Tykerb), or pentuzumab (Perjeta) should be
considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate
drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as

high-dose chemotherapy with stem cell transplant.
Post-Treatment Care
The American Society of Clinical Oncology (ASCO) recommends follow-up care for patients
who have been treated for breast cancer:
Visit your doctor every 3 - 6 months for the first 3 years after your first cancer
treatment, every 6 - 12 months during the fourth and fifth year, and once a year
thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but
no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a

mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report
any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your
care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule
follow-up visits for re-evaluation of your treatment.
ASCO does not recommend the use of laboratory blood tests (complete blood counts,
carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDGPET scan, CT scan) for routine breast cancer follow-up.
Genetic counseling may be helpful if you have:
Ashkenazi Jewish heritage

Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast
cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed

with breast cancer
History of breast cancer in a male relative
Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how
long a woman should wait to become pregnant after breast cancer treatment. Because of the
connection between estrogen levels and breast cancer cell growth, some doctors recommend
delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer
recurrence and improve odds for survival. However, other studies indicate that conceiving 6
months after treatment does not negatively affect survival. Discuss with your doctor your risk
for recurrence, and when it may be safe to attempt pregnancy.
Recurrent Breast Cancer

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has
come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years
after treatment, but breast cancer can recur many years later. Treatment options are based on
the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and
the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent
cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.
Because most breast cancer recurrences are discovered by patients in between doctor visits, it
is important to notify your doctor if you experience any of the following symptoms. These
symptoms may be signs of breast cancer recurrence:
New lumps in the breast

Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge
Surgery
Surgery is a part of nearly every patient's treatment for breast cancer. The initial surgical
intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy
(the removal of the breast) was the standard treatment for nearly all breast cancers. Now,
many patients with early-stage cancers can choose breast-conserving treatment, or
lumpectomy followed by radiation, with or without chemotherapy.
For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined
with radiation therapy works as well as a modified radical mastectomy.
Breast-Conserving Procedures
Breast-conserving procedures are considered as appropriate and as successful as mastectomy
in most women with early stage breast cancer. All women should discuss these options fully
with their doctor. Recurrence rates with conservative surgery are highest in women under age
45. Some women choose mastectomy over breast-conserving treatment even if the latter is
appropriate because it gives them a greater sense of security and allows them to avoid
radiation therapy.
Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the
armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for
small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with
breast radiation therapy, to remove additional tissue (should the margins of the specimen
show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation
therapy is appropriate and as effective as mastectomy for most women with stage I or II
breast cancers.
Click the icon to see an illustrated series detailing breast lump removal surgery.
Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes

referred to as quadrantectomy) removes the cancer and a large area of breast tissue,
occasionally including some of the lining over the chest muscles. It is less invasive than a full
mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Studies
have found that breast-conserving surgeries plus postoperative radiotherapy offer the same
survival rates as radical mastectomy in most women with early breast cancer.
Mastectomy
Surgery to remove the breast (mastectomy) is important for women with operable breast
cancer who are not candidates for breast conserving surgeries. There are different variations
on the procedure:
A total mastectomy involves removal of the whole breast and sometimes lymph
nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes
under the arm, and some additional fat and skin. (A modified radical mastectomy
removes the entire breast and armpit lymph nodes, with the underlying chest wall
muscle.) For most patients, there are no survival advantages from radical
mastectomy compared to less invasive mastectomies.
Click the icon to see an illustrated series detailing mastectomy surgery.
Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area
of the procedure, and pain relievers may be necessary.
The most frequent complication of extensive lymph node removal is lymphedema, or
swelling, of the arm. The likelihood of edema can be lessened by removing only some of the
lymph nodes instead of all of them.
Infrequent complications include poor wound healing, bleeding, or a reaction to the

anesthesia.
After mastectomy and lymph node removal, women may experience numbness, tingling, and
difficulty in extending the arm fully. These effects can last for months or years afterward.
Breast Reconstruction
After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction,
which can be performed at the time of the mastectomy itself, if desired. Several studies have
indicated that women who take advantage of cosmetic surgery after breast cancer have a
better sense of well-being and a higher quality of life than women who do not choose
reconstructive surgery.
The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is
taken from elsewhere in the body. Muscle flap procedures are more complicated, however,
and blood transfusions may be required. If the nipple is removed, it is rebuilt from other body
tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast
that is identical to its partner, and additional operations may be necessary to achieve a
desirable effect.
Implants, including silicone implants, do not appear to put a woman at risk for breast cancer
recurrence. However, breast implants are not lifetime devices. About half of women who
receive an implant for breast reconstruction will need to have it removed or replaced about 10
years after implantation.
Click the icon to see an illustrated series detailing breast reconstruction surgery.
Radiation
Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor
in the breast or surrounding tissue. It is used for several weeks following lumpectomy or
partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce
the chance of breast cancer recurrence in the breast and chest wall. Radiation is also
important in advanced stages of cancer for relief of symptoms and to slow progression.
Research shows that radiation therapy is helpful for women of all ages, including those over
age 65.
Administration of Radiation Therapy

Radiation is generally administered in the following ways:
External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and
delivered externally by an x-ray machine that targets radiation to the whole breast. It may be
delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or
lymph node involvement). The treatment is generally given daily (except for weekends) for
about 6 weeks. Some hospitals offer a shortened course of 3 weeks of radiation for patients
with early-stage breast cancer.
Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy).
Implants are most often used as a radiation boost after whole breast radiation.
Side Effects of Radiation Therapy

Side effects of radiation include:
Fatigue is very common and increases with subsequent treatments, but most women
are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a
corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated
sessions, the skin may become moist and "weepy." Exposing the treated skin to air
as much as possible helps healing. Washing the affected skin with soap and water is
not harmful.
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.
Long-Term Complications
Future complications include:
Radiation to the left breast may increase the long-term risk for developing heart
disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in
younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft
tissue malignancies known as sarcomas.
Current advanced imaging techniques use precise radiation that reduces exposure. These
newer techniques are likely to reduce the risks for heart disease and other serious
complications.
Chemotherapy
Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by
injection. They work systemically by killing cancer cells throughout the body.
(Unfortunately, they also kill some normal cells, which accounts for many of their side
effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to
treat types of early-stage breast cancer.
Newer biologic drugs target specific proteins involved in cancer. Treatment with these drugs
is called targeted therapy. Because targeted therapy drugs do not work as systemically as
chemotherapy or hormone-blocking drugs, they tend to cause fewer widespread side effects,
although they also carry risks of their own
Chemotherapy needs to be tailored to the type of cancer involved. Women require different
treatments depending on whether the tumor is node-negative or -positive, hormone receptorpositive or -negative, or HER2-positive or -negative. Different treatment approaches are also
used for early-stage cancer and advanced cancer.
Adjuvant chemotherapy is administered following surgery and before radiation therapy.
Delaying chemotherapy until more than 12 weeks after surgery may increase the risk for
breast cancer recurrence and reduce the odds for survival.
Chemotherapy Drug Classes

Many different types of chemotherapy drugs are used to treat breast cancer. Common types
of chemotherapy drug classes include:
Anthracyclines include doxorubicin (Adriamycin, generic) and epirubicin (Ellence,

generic). Anthracycline-based combination regimens are often used to treat earlystage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol, generic) and docetaxel (Taxotere, generic). These
drugs may be particularly helpful for node-positive breast cancer. A newer
formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced
breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin, generic) and carboplatin
(Paraplatin, generic). These drugs may be used in combination regiments for
advanced cancer or for cancers associated with BRCA genes.
Chemotherapy Regimens for Early-Stage Breast Cancer

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug
classes rather than drug names. For example, regimens that contain an anthracycline drug
(such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as
docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and
methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy
regimens.
Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months.
Common chemotherapy regimens for early-stage breast cancer include:
AC (Doxorubicin and cyclophosphamide)

AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)
Chemotherapy for Advanced (Metastatic) Cancer

Patients who develop metastatic disease (cancer that spreads throughout the body) are
generally not curable. New advances in drug therapies, however, can help shrink tumors,
prolong survival, and improve quality of life.
Chemotherapy regimens for advanced cancer may use a single drug or a combination of
drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for
advanced breast cancer. Some specific individual drugs and combinations for advanced
cancer include:
Gemcitabine and paclitaxel. Gemcitabine (Gemzar, generic) is used in combination

with paclitaxel (Taxol, generic) as a first-line treatment option for women with
metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere, generic). Capecitabine is an oral
drug that is chemically related to 5-FU. In addition to combination treatment with
docetaxel, it is used in combination with a new type of drug, ixabepilone (Ixempra),
for patients with advanced breast cancer who have not responded to other types of
chemotherapy. It is also being studied in combination with other drugs.
Eribulin (Halaven) was approved in 2010 as a treatment for metastatic breast cancer
in patients who have already received at least two regimens of chemotherapy for
late-stage disease. The injectable drug is a synthetic compound of a chemical found
in a type of sea sponge.
Everolimus (Afinitor) was approved in 2012 for treatment of advanced hormone

receptor-positive, HER2-negative breast cancer.
Numerous chemotherapy drugs and drug combinations are being tested in clinical trials.
Patients with advanced breast cancer may also receive other types of drug treatments. For
example, bisphosphonate drugs such as zoledronic acid (Zometa) and pamidronate (Aredia,
generic), and the biologic drug denosumab (Xgeva), are important supportive drugs for
preventing fractures and reducing pain in people whose cancer has spread to the bones.
Targeted Therapy for Early-Stage HER2-Positive Breast Cancer

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody biologic drug that targets
the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage
breast cancer and are associated with more aggressive disease. Younger women tend to be
most affected.
Trastuzumab is given along with other chemotherapy drugs following lumpectomy or
mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and
death among women with early-stage breast cancer, but it increases the risk of heart
problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart
muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to
have regular heart monitoring, especially if they have already have heart problems.
Targeted Therapy for Advanced HER2-Positive Breast Cancer

Three targeted therapy (biologic) drugs are approved for the treatment of HER2-positive
advanced breast cancer:
Trastuzumab (Herceptin) is used after chemotherapy, along with drugs such as

paclitaxel.
Lapatinib (Tykerb) is used in combination with capecitabine (Xeloda). Research
suggests it may have fewer risks for heart problems than trastuzumab. Lapatinib is
also approved for combination use with letrozole (Femara, generic) as a first-line
treatment for hormone-positive and HER2-positive advanced breast cancer in
postmenopausal women for whom hormone treatment is recommended.
Pentuzumab (Perjeta) is used in combination with trastuzumab and docetaxel for
treatment of HER2 postive metastatic breast cancer. Pentuzumab is the newest type
of anti-HER2 therapy.
Side Effects of Chemotherapy

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses
and increase over the course of treatment.
Common side effects include:
Nausea and vomiting. Drugs such as ondansetron (Zofran, generic) and aprepitant
(Emend) can help relieve these side effects.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Serious short- and long-term complications can also occur and may vary depending on the
specific drugs used. They may include:
Anemia. Chemotherapy-induced anemia is usually treated with erythropoiesisstimulating drugs, which include epoietin alfa (Epogen, Procrit) and darberpetin alfa
(Aranesp). Doctors need to follow strict dosing guidelines when administering these
drugs. Patients should discuss the risks and benefits of erythropoiesis-stimulating
drugs with their oncologists. [For more information, see In-Depth Report #57:
Anemia.]
Increased chance for infection from severe reduction in white blood cells
(neutropenia). The addition of a drug called granulocyte colony-stimulating factor
(filgrastim and lenograstim) can help reduce the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause is a common side

effect of chemotherapy. A hormone medication called a gonadotropin-releasing
hormone analogue, which puts women in a temporary pre-pubescent state during
chemotherapy, may preserve fertility in some women. Women may also wish to
consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro
fertilization and freezing of embryos for later use. The American Society of Clinical
Oncology recommends that women being treated for cancer see a reproductive
specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
Some women report problems in concentration, motor function, and memory, which
can be long-term.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure,
particularly in women with pre-existing risk factors. Cumulative doses of
anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time
and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart
and central nervous system. Taxane therapy may also cause severe joint and muscle
pain in some patients.
Hormone Therapy
The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is
recommended for women whose breast cancers are hormone-receptor positive (either
estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread
to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for
patients with hormone receptor-positive ("hormone sensitive") tumors. Different types of
hormone therapy work in different ways by:
Blocking estrogen receptors in cancer cells (Tamoxifen)

Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)
Tamoxifen was the first widely used hormonal therapy drug, but today it is mainly used as
adjuvant therapy for premenopausal and perimenopausal women with hormone-sensitive
breast cancer. Postmenopausal women are now usually prescribed aromatase inhibitors.
Tamoxifen and Selective Estrogen Receptor Modulators (SERMs)

Tamoxifen (Nolvadex, generic) has been the standard hormonal drug used for breast cancer.
It belongs to a class of compounds called selective estrogen receptor modulators (SERMs).
SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in
place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth.
Because SERMs block estrogens effects on cancer cells, they are sometimes referred to as
"anti-estrogen" drugs.
Tamoxifen is used for all cancer stages in (mainly premenopausal) women with hormone
receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women.
Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer,
but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in
a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is
approved only for postmenopausal women with hormone-sensitive advanced breast cancer in
whom tamoxifen or aromatase inhibitors no longer work.
To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery
and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side
effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial)
cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a
symptom of uterine cancer. Tamoxifen risks for blood clots may be higher for obese women.
Tamoxifen interacts with certain types of antidepressants. In particular, the antidepressants
paroxetine (Paxil, generic) and fluoxetine (Prozac, generic) can weaken the effectiveness of
tamoxifen. Doctors recommend venlafaxine (Effexor, generic) as a first-line antidepressant
drug for women who take tamoxifen.
Less serious, but discomforting, side effects include hot flashes and mood swings. According
to one study, nearly 25% of women stop taking tamoxifen within 1 year because of these
symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years,
however, increases the risk for cancer recurrence and death. Talk with your doctor about
antidepressants or other therapies that may help you cope with tamoxifens side effects.
The American Society of Clinical Oncology (ASCO) current guidelines recommend that
postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen
therapy. Postmenopausal women who have already completed 5 years of tamoxifen therapy
can benefit from switching to an aromatase inhibitor for up to an additional 5 years to help
further reduce their risk of cancer recurrence. Several recent studies have indicated that
switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and
reduces the risk of death from breast cancer as well as other causes.
Aromatase Inhibitors
Aromatase inhibitors are recommended as first-line adjuvant therapy for postmenopausal
women with hormone-sensitive breast cancer. Aromatase inhibitors are taken for up to 5
years. They can be used either before or after tamoxifen treatment. (If women begin and then
discontinue aromatase inhibitors, they should consider switching to tamoxifen to complete
the 5-year treatment.)
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many
major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work
differently than tamoxifen. Tamoxifen interferes with tumors ability to use estrogen by
blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen
in the body.
Because these drugs cannot stop the ovaries of premenopausal women from producing
estrogen, they are recommended only for postmenopausal women.
There are currently three aromatase inhibitors approved for treating early-stage, hormone
receptor-positive breast cancer in postmenopausal women:
Anastrazole (Armidex, generic)

Exemestane (Aromasin, generic)
Letrozole (Femara, generic)
There are no significant differences between these three drugs. Women who cannot tolerate
one type of aromatase inhibitor can switch to a different one. All of these drugs are also
approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies
indicate that the introduction of aromatase inhibitors has helped greatly in prolonging
survival for women with advanced cancer.
Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine
cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone
loss and fractures. Women should have their bone mineral density monitored during
aromatase inhibitor treatment. In general, recent studies indicate that aromatase inhibitors are
better than tamoxifen in improving survival and reducing the risk of cancer recurrence.
Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.
Ovarian Ablation
Ovarian ablation is a treatment that stops estrogen production from the ovaries. Medications
can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also
shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but
several therapies are available to help prevent bone loss.)
Chemical Ovarian Ablation. Drug treatment to block ovarian production of estrogen is called
chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing
hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also
sometimes called GnRH agonists). These drugs block the release of the reproductive
hormones LH-RH, therefore stopping ovulation and estrogen production.
Bilateral Oophorectomy. Bilateral oophorectomy, the surgical removal of both ovaries, is a
surgical method of ovarian ablation. It may modestly improve breast cancer survival rates in
some premenopausal women whose tumors are hormone receptor-positive. In these women,
combining this procedure with tamoxifen may improve results beyond those of standard
chemotherapies. Oophorectomy does not benefit women after menopause, and its advantages
can be blunted in women who have received adjuvant chemotherapy. The procedure causes
sterility.
Resources
www.cancer.gov -- National Cancer Institute

www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.breastcancer.org -- BreastCancer.Org
www.komen.org -- Susan G. Komen Breast Cancer Foundation
www.nccn.org -- National Comprehensive Cancer Network
www.cancer.net -- Cancer.Net
www.cancer.gov/clinicaltrials -- Find clinical trials
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Version Info
Last Reviewed on 12/21/2012

Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard
Medical School; Physician, Massachusetts General Hospital. Also reviewed by David
Zieve, MD, MHA, Medical Director, A.D.A.M. Health Solutions, Ebix, Inc
Source: Breast cancer | University of Maryland Medical Center

http://umm.edu/health/medical/reports/articles/breast-cancer#ixzz2YFcEPUY6
University of Maryland Medical Center
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JAKARTA, 5 JULI 2013

Understanding Breast Cancer What Is Breast Cancer?

What Is Breast Cancer?

Breast cancer is an uncontrolled growth of breast cells. To better understand breast

Breast AnatomyLarger Version

Stages of Breast Cancer

Inflammatory breast cancer is considered at least stage IIIB.

A womans risk of breast cancer approximately doubles if she has a first-degree

Understanding Breast Cancer Breast Cancer Risk and Risk Factors

Breast Cancer Risk and Risk Factors

Risk of Developing Breast Cancer

Risk of Developing Breast Cancer

From age 50 to 59, absolute risk is 1 in 38, or 2.6%.

From age 60 to 69, absolute risk is 1 in 27, or 3.7%.

Example of breast cancer risk going up

Example of breast cancer risk going down

Medical researchers might express it this way:

.5 means that your risk decreases by half, or 50%

Breast Cancer Risk Factors

Risk factors you can control

regularly drinking alcohol

Risk factors you cant control

starting menstruation (monthly periods) at a young age (before age 12)

exposure to estrogens in the environment (such as hormones in meat or pesticides

The Clinical Problem

breast cancer increases with age (Figure 1Figure 1

factors (Table 1Table 1

Risk Factors for Breast Cancer.).

Strategies and Evidence for Screening

Women 50 to 69 Years of Age

50s and 32% for those in their 60s (Table 2Table 2

Women 70 Years of Age or Older

Women 40 to 49 Years of Age

Risks and Costs of Screening

Relevance and Generalizability of Data from Randomized Trials

Value of Other Screening Methods

examinations in the clinic or by the patient herself (Table 4Table 4

Conclusions and Recommendations

Breast cancer: prevention and control

demonstration areas. Mammography screening is very costly and is recommended for

Breast cancer burden

Breast cancer risk factors

Breast cancer control

early diagnosis or awareness of early signs and symptoms in symptomatic

screening that is the systematic application of a screening test in a presumably

A screening programme is a far more complex undertaking that an early diagnosis

Breast self examination (BSE)

About Us Careers Ways You

Find a Doctor Make an Appointment

Centers and Services

Medical Reference: Medical Encyclopedia Spanish Medical Encyclopedia Drug

Print the Page

Medical Reference Guide

In-Depth Patient Education Reports

FDA Withdraws Bevacizumab (Avastin)for Breast Cancer

Pentuzumab (Perjeta) is the newest treatment for advanced HER2-positive breast

Breast cancer is either noninvasive (referred to as in situ, confined to the site of

Noninvasive Breast Cancer

Invasive Breast Cancer

Click the icon to see an image of the breast.

Race and Ethnicity

Family and Personal History

Estrogen-progestogen therapy (EPT) is used by women who have a uterus, because