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Adjuvant systemic therapy in early-stage breast cancer

Agents used in adjuvant breast cancer systemic therapy include the following:
Taxanes: Among the most active and commonly used chemotherapeutic agents for the treatment of early stage breast
cancer
Anthracyclines: Used in the treatment of early stage breast cancer for decades, although concerns regarding
anthracycline-associated cardiotoxicity or leukemogenic potential remain
Pertuzumab: Use in combination with trastuzumab and chemotherapy as adjuvant treatment of patients with HER2-
positive early breast cancer at high risk of recurrence
Trastuzumab: Used in the (neo)adjuvant treatment in patients with HER2-positive breast cancer
Tamoxifen positive breast cancer; decreases estrogen's ability to
stimulate existing micrometastases or dormant cancer cells
Aromatase inhibitors (AIs): Inhibit aromatase, the enzyme responsible for converting other steroid hormones into
estrogen
If a tumor has this property, it is called HER2-positive. HER2 positive cancers are more aggressive than HER2 negative cancer.
ER positive/HER2 negative breast cancer, tumors that are
 ER positive are much more likely to respond to treatments that block estrogen. Treatment possibilities include
selective estrogen-receptor response modulators (SERMs), aromatase inhibitors, estrogen-receptor downregulators
(ERDs) and luteinizing hormone-releasing hormone agents (LHRHs).
 HER2 negative cancers will not respond to treatment with drugs that target HER2, such as trastuzumab (Herceptin)
and lapatinib (Tykerb)
 The most common treatment for ER positive and HER2 negative breast cancer is hormone blocking therapy.
Although chemotherapy can also be used, no specific type is recommended by the American Society for Clinical
Oncology (ASCO). Available drugs can include taxanes, anthracyclines, platinum-based drugs, capecitabine (Xeloda),
eribulin (Halaven), gemcitabine (Gemzar), ixabepilone (Ixempra), and vinorelbine (Navelbine).
 The prognosis for patients with ER+ and HER2- breast cancer depends on how advanced the cancer was when it was
detected. Prognosis is also influenced by the size of the tumor and if the cancer has spread to other organs.
 Most women with very early stage breast cancers will live a normal lifespan. Five-year survival rates are based on the
stage (0-4) of breast cancer according to the American Cancer Society, with stage 4 at 22% and stage 0 at 100%.
Stage 4 is metastatic breast cancer, which means that cancerous cells have spread to other regions of the body.
 Overall, estrogen receptor-positive breast cancer is treatable, especially when diagnosed early.

ER-negative and/or HER2-positive


You may have hormone therapy after surgery, chemotherapy, and radiation are finished. These treatments can help prevent a
return of the disease by blocking the effects of estrogen.
 The medication tamoxifen (Nolvadex, Soltamox) helps stop cancer from coming back by blocking hormone receptors,
v b .I ’ taken for up to 5 years after initial treatment for breast
cancer
 A class of medicines called aromatase inhibitors actually stops estrogen production. These include
anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). T y’ ly u w w ’v l y
through menopause.
 CDK 4/6 inhibitors palbociclib (Ibrance) and ribociclib (Kisqali) are sometimes used with aromatase inhibitors in women
with certain types of advanced breast cancer who have gone through menopause. Abemaciclib (Verzenio) and
palbociclib can sometimes be used with the hormone therapy fulvestrant (Faslodex).
*palbociclib - Take this medication by mouth with food as directed by your doctor,
- usually once daily for 21 days, then stopping the medication for 7 days. This is one cycle of treatment.
- Continue taking the medication this way as directed by your doctor. Swallow the capsules whole. Do not
crush, chew, or open the capsules. Do not take capsules that are broken or look damaged. If you vomit
after taking the medication, do not take another dose of the medication that day. Take the next dose at
the usual time the next day.
- The dosage is based on your medical condition, laboratory tests, response to treatment, and other
medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use
(including prescription drugs, nonprescription drugs, and herbal products). Your doctor may stop your
medication for a while or reduce your dose if you get any side effects. Talk to your doctor for more details.
- Grapefruit can increase the chance of side effects with this medicine.
- Side Effects: Nausea, vomiting, loss of appetite, diarrhea, tiredness, weakness, hair loss, mouth sores, or
numbness/tingling of arms/legs may occur. If any of these effects persist or worsen, tell your doctor or
pharmacist promptly.
Lapatinib is used together with another medication (capecitabine) to treat a certain type of breast cancer (HER2-
positive) that has not responded to the standard treatment. Lapatinib may also be used together with another
medication (letrozole) to treat HER2-positive breast cancer in women after menopause. It works by slowing or
stopping the growth of cancer cells.
- Take this medication by mouth 1 hour before or 1 hour after a meal, usually once daily or as directed by your
doctor. It is important that you do not take this medication more than once daily.
- Nausea, vomiting, upset stomach, mouth sores, mild rash, dry skin, and trouble sleeping may occur. Diarrhea
is a common side effect and may become severe. Tell your doctor right away if diarrhea occurs or if you have
signs of a severe loss of body water (dehydration) such as dizziness or decreased urination.
- Treatment with this drug may sometimes cause your hands/feet to develop a skin reaction called hand-foot
syndrome (palmar-plantar erythrodysesthesia).

* lapatinib (Rx) Classes: Antineoplastics, Tyrosine Kinase Inhibitor; Antineoplastics, Anti-HER2; Antineoplastics, EGFR
Inhibitor
Brand and Other Names:Tykerb
tablet :250mg
HER2-overexpressing metastatic breast cancer
Indicated in combination with capecitabine for treatment of patients with advanced or metastatic
breast cancer whose tumors overexpress HER2 and who have received prior therapy including an
anthracycline, a taxane, and trastuzumab
 1250 mg PO qDay on Days 1-21 continuously in combination with capecitabine (2000
mg/m²/day PO divided q12hr) on Days 1-14 in a repeating 21-day cycle
Hormone-positive and HER2-positive advanced breast cancer
Indicated in combination therapy with letrozole for treatment of postmenopausal women with
hormone receptor-positive and HER2-positive breast cancer for whom hormonal therapy is indicated
 1500 mg PO qDay administered continuously in combination with letrozole 2.5 mg PO qDay
dosage modification:
 Diarrhea be reintroduced at a lower dose
 Concomitant strong CYP3A4 inhibitors: Reduce the dose to 500 mg/day
 Severe hepatic impairment
- HER2 positive metastatic breast cancer: Reduce dose from 1250 mg/day to 750 mg/day
- Hormone receptor positive, HER2 positive breast cancer: Reduce dose from 1500 mg/day to
1000 mg/day
Contraindicated

https://reference.medscape.com/drug/tykerb-lapatinib-342235#3
capecitabine (Rx)
Brand and Other Names:Xeloda
Classes: Antineoplastics, Antimetabolite
tablet 150mg,500mg
Breast Cancer
Metastatic, resistant to paclitaxel, anthracyclines
Monotherapy: 1250 mg/m² BID for 2 weeks q3Weeks
Combo therapy with Docetaxel: 1250 m² PO BID for 2 weeks q3Weeks plus docetaxel 75 mg/m² 1 hour IV infusion
q3Weeks
Administration
Swallow with water within 30 min after a meal
Dosage may need to be individualized to optimize patient management
Dose Modifications
Renal impairment - CrCl 30-50 mL/min: Reduce dose by 25%
- CrCl <30 mL/min: Contraindicated

standard.

Docetaxel -moa: Inhibits mitosis


apply: Breast cancer, non-small cell lung cancer, prostate cancer, gastric cancer, head and neck cancer,
ovarian cancer, bladder cancer
acute: Hypersensitivity
delayed: Neurotoxicity, fluid retention, myelosuppression with neutropenia

Doxorubicin -Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks; inhibits
topoisomerase II; intercalates into DNA:
apply: B ,H k ’ non-H k ’ ly , u sarcoma, ovarian cancer,
non-small cell and small cell lung cancer, y ,Wl ’ u , neuroblastoma
acute toxicity: Nausea, red urine (not hematuria)
delayed: Cardiotoxicity (see text), alopecia, myelosuppression, stomatitis

Cyclophosphamide - MOA:Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
- apply to: Breast cancer, ovarian cancer, non-H k ’ ly , CLL, soft tissue sarcoma,
neuroblastoma, W l ’ u , b y
acute toxicity: Nausea and vomiting
delayed: Moderate depression of peripheral blood count; excessive doses produce severe
bone marrow depression with leukopenia, thrombocytopenia, and bleeding; alopecia
and hemorrhagic cystitis occasionally occur with cyclophosphamide;