Metastatic breast cancer treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Assistant Editor-in-Chief Jack Khouri

Overview

With rare exception, metastatic breast cancer is an incurable but treatable illness. Currently, it is managed as a chronic disease, especially the category that is ER-positive with predominantly bone or soft tissue metastasis. Chemotherapy, biologic therapy and endocrine therapy are all considered in the treatment of metastatic breast cancer.

Principles of therapy

• The main aims of therapy are prolonging survival, improving quality of life and avoiding treatment-induced toxicity. Given that treatment is palliative, patients should be given treatment holidays in order to reduce drug-induced toxicity.
• HER2 overexpression and hormone receptor status are very important factors that guide therapy and influence prognosis.
• Multiagent chemotherapy regimens don't show significant survival benefit compared to single-drug regimens and augment toxicity.
• Chemotherapy is recommended for patients with ER-negative metastatic breast cancer and those with ER-positive breast cancer resistant to endocrine therapy or associated with visceral disease.
• Trastuzumab increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2.
• Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 overexpression.

Chemotherapy

• the most active single agents are Anthracyclines (Doxorubicin 60-75 mg/m2 IV every 21 days), Taxanes (paclitaxel 175 mg/m2 every 21 days or 80 mg/m2 IV days 1,8,15 every 21 days; docetaxel 60-100 mg/m2 IV every 21 days), Capecitabine (1000-1250 mg/m2 PO twice a day on days 1-14 every 21 days), Gemcitabine (800-1200 mg/m2 IV days 1,8,15 every 28 days), and Vinorelbine (25 mg/m2 weekly or days 1,8,15 every 28 days)
• Bevacizumab has been shown to improve the efficacy of taxanes in frontline treatment of patients with metastatic breast cancer.
• Combination chemotherapy include Gemcitabine combined with paclitaxel and docetaxel ombined with capecitabine.
• There is little evidence from trials reported from 2000 to 2007 that major survival differences exist between many commonly employed chemotherapy regimens.
• Trastuzumab should be added to chemotherapy. If progression of disease occurs, Lapatinib and capecitabine are recommended concomitantly.

Endocrine Therapy

• Endocrine therapy is based on the fact that estrogen receptor-positive tumors are highly estrogen-dependent for growth.
• Endocrine therapy agents for breast cancer are meant to block the effect the estrogen growth effect on breast cancer cells via several mechanisms:
  • Blocking the estrogen receptor (eg, Selective Estrogen Receptor Modulators like Tamoxifen)
  • Down-regulating and degrading the estrogen receptor (eg, Fulvestrant which is a pure estrogen antagonist)
  • Decreasing estrogen synthesis by blocking the enzyme called Aromatase, which converts androgens to estrogens. Aromatase inhibitors include many agents like Anastrozole, Letrozole and Exemestane
  • Decreasing estrogen level by:
    • Shutting down the hypothalamus-pituitary-ovarian axis by means of GnRH agonists, which block the hypothalamic signal that normally promotes etrogen synthesis by the ovaries
    • Ablating the ovaries (oophorectomy)
• Endocrine therapy should be the first-line treatment for ER-positive metastatic breast cancer unless the patient has vital organ are involved(the so-called visceral crisis (ie, liver or lung disease)) where first-line chemotherapy should be offered first.
• There is no survival advantage for the combined administration of chemotherapy and endocrine therapy over either single therapy.