Update on Breast Care

M. Bernadette Ryan, M.D., FACS Head, Section of Surgical Oncology May 18, 2009

Outline
ANDI concept in benign breast disease
myatalgia

Breast imaging for screening & diagnosis Breast Cancer

1/2009 update in NCCN guidelines PBI Oncotype Dx

ANDI
Aberrations of normal development and involution concept of benign disorders based on pathogenesis First published by Hughes et al. in 1987 in Lancet Embraced slowly in the USA

ANDI - 2
Bi-directional framework Horizontal axis: main clinical presentation
normal - aberration - disease

Vertical axis: stages in development

early reproductive (15-25 years) mature reproductive (25-40 years) involution (35-55 years)

ANDI - 3
Normal Process Early Reproductive 15-25 years Mature Reproductive 25-40 years
Lobular development Stromal development Nipple eversion

Aberration
Fibroadenoma Adolescent hyperplasia Nipple inversion

Disease
Giant FA or multiple FAs Gigantomastia Subareolar abscess/ mammary duct fistula Incapacitating mastalgia

Cyclic changes

Cyclic mastalgia Nodularity Ductal papilloma Bloody nipple discharge Macrocysts, adenosis, sclerosing lesions Ductal ectasia Nipple inversion Hyperplasia

Epithelia hyperplasia of pregnancy Lobular involution microcysts Duct involution dilation sclerosis Epithelial turnover

Involution 35-55 years

Periductal mastitis/ abscess Atypia

Non - ANDI
Fat necrosis Lactational abscesses Contributions of smoking and oro-nipple contact in non-puerperal abscesses True neoplasms: phyllodes tumor, tubular adenoma, lipoma, etc. Mondors disease, diabetic mastopathy,

Mastalgia
Probably hormonally related
usually cyclic and ends with menopause responds to hormone treatment

Many theories:
increased estrogen decreased progesterone increased prolactin increased end-organ response low prostaglandin E1 due to EFA deficiency

Mastalgia - 2
Cyclic or non-cyclic breast pain
rule out chest wall source in non-cyclic rule out significant lesion with imaging
localized pain may be due to cancer, cyst, sclerosing lesion

Treatment
Reassurance if mild Reassurance and primrose oil if moderate Add drugs if severe (interferes with lifestyle)

Mastalgia - 3
Cyclic Pain Primrose oil
1000-1500 BID

Non-Cyclic 27% 30% 56% 20% 10-40%

44-58% 70-80% 80-90%

Danazol
10 mg QD

200-400 mg QD

Tamoxifen
2.5 mg BID

Bromocriptine 47% Placebo 10-40%

Breast Imaging
Mammograms Ultrasound MRI PET scans

Mammograms
Annual screening beginning at age 40
as young as 25 in high risk groups upper limit not established

Digital mammogram may be better especially in young women and older women with dense breasts Mobile units may increase compliance

Ultrasound
Initial diagnostic tool in women < 30-35 with symptoms or palpable findings Adjunct to mammography
diagnostic w/u biopsy

May be used with mammogram to screen women at high risk or with dense breasts
no PRS showing survival benefit

MRI - screening
Screen high risk women
BRCA 1 or 2, TB53 or PTEN mutations First degree relative with above & untested Lifetime risk 20-25% by model based on FHx Chest irradiation between ages 10 & 30

Role in women at lesser risk uncertain

LCIS, AH, prior breast cancer, 15-20% risk

Not recommended in average risk women

BRCAPRO
Free programs available Need extensive family history
age of diagnosis of cancer as well as current age or age of death of relatives

Calculates risk of harboring BrCa gene and risk of developing breast & ovarian cancer

BRCAPRO - 2

BRCAPRO - 3

BRCAPRO - 4

MRI - diagnostic
Define extent of disease before BCS
leads to higher mastectomy rate without clear benefit in local control or survival

Define extent of disease before & after neoadjuvant therapy Look for additional primaries Look for occult primary
Pagets disease & isolated nodal metastases

PET scan
NCCN recommends against use in stage IIII disease
Biopsy of equivocal or suspicious sites is more likely to provide useful information

Lobular cancer frequently PET negative Not useful to stage axilla overall role in breast cancer unclear

NCCN updates: DCIS

Minimum margin is still 1 mm
generally decreased failure rates with wider margins up to 10 mm post-excision mammogram if uncertainty

Recommends against sentinel node biopsy

reasonable for mastectomy

Excision alone in low risk disease

radiation reduces local failure by 50% equivalent survival

NCCN: invasive cancer w/u

Genetic counseling if high risk MRI optional No PET or PET/CT ER/PR and Her 2: use a reliable lab Imaging to rule out metastases only if symptomatic
may consider in locally advanced disease

NCCN - local treatment

Negative margin not defined Focally + margin acceptable if no EIC
consider higher XRT boost to tumor bed

> 70, T1N0M0, ER/PR +

reasonable to treat with lumpectomy & tamoxifen or an aromatase inhibitor can be cN0 or pN0

NCCN - neoadjuvant
In Stage II & T3N1: only if pt wants BCS Use in all other Stage III Consider AI if post-menopausal & ER/PR positive cN+: confirm with needle biopsy
Level I & II dissection regardless of response

cN-: SNBx pre- or post-chemo

AxD if +

NCCN - Radiation
Radiation can be with or without a boost
boost: < 50, close margins, + nodes or LVI

PBI discouraged outside of a trial Post-mastectomy XRT unchanged:

>/= 4 + nodes, >5 cm, margins < 1mm or + consider in 1-3 nodes

Base XRT on initial clinical stage in neoadjuvant patients

Partial Breast Irradiation

Low risk women
age > 45, tumor </= 3 cm, negative margins & nodes (? DCIS)

Potential advantages
shorter treatment course
can give prior to chemotherapy may improve access to BCS

? better cosmesis Need PRTs to compare failure rates

PBI - 2
Treat tumor bed with 1 cm margins Intra-op: single fraction Post-op:
BID x 10 fractions with total dose 34-38.5 Gy
MammoSite and other balloons after loading catheters external beam with 3D conformal/IMRT

NCCN - adjuvant treatment

ER/PR + & Her 2 -: consider Oncotype Still little data on chemo in women > 70
individualize considering co-morbidities

No prospective randomized data on use of Herceptin in tumors < 1 cm & node but considered reasonable

Baseline & f/u DEXA scans if treat with AI or if menopause induced by treatment

T1/2, ER/PR+, node -, her 2adjuvantonline

age, health, size, grade, nodes, ER/PR odds of death or recurrence at 10 years odds of benefit from adjuvant treatment

Oncotype Dx
21 gene test on paraffin blocks recurrence score: correlates with 10-year relapse in tamoxifen-treated patients and with benefit from chemotherapy

Tailor X
PRT to determine value of Oncotype Low RS (1-10): tamoxifen or AI High RS (> 26): chemotherapy and tamoxifen or AI Intermediate RS (11-25): randomize between 2 treatments above Off study, 18-30 considered intermediate
about $3000 (some insurances cover test)

Future
Greater effort to tailor treatment to individual to avoid toxicity without jeopardizing survival Pay for performance
accredited breast centers adherence to national guidelines volume of breast cases

Comments or questions?