Metastatic breast cancer treatment: Difference between revisions
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***Affecting the hypothalamus-pituitary-ovarian axis by GnRH agonists, which block the hypothalamic signal that normally promotes etrogen synthesis by the ovaries | ***Affecting the hypothalamus-pituitary-ovarian axis by GnRH agonists, which block the hypothalamic signal that normally promotes etrogen synthesis by the ovaries | ||
***Ablating the ovaries (oophorectomy) | ***Ablating the ovaries (oophorectomy) | ||
*In general, all patients with hormone receptor-positive advanced disease should be offered endocrine therapy as the initial systemic approach unless the patient is suffering a visceral crisis (ie, rapidly progressive liver or parenchymal lung disease) in which case first-line chemotherapy is appropriate | |||
== References == | == References == | ||
Revision as of 14:41, 1 December 2011
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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.[1]
- Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 overexpression.[2]
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.[3]
- Combination chemotherapy include Gemcitabine combined with paclitaxel and docetaxel ombined with capecitabine.
- 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 by degrading the estrogen receptor (eg, Fulvestrant which is a pure estrogen antagonist)[4]
- 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:
- Affecting the hypothalamus-pituitary-ovarian axis by GnRH agonists, which block the hypothalamic signal that normally promotes etrogen synthesis by the ovaries
- Ablating the ovaries (oophorectomy)
- In general, all patients with hormone receptor-positive advanced disease should be offered endocrine therapy as the initial systemic approach unless the patient is suffering a visceral crisis (ie, rapidly progressive liver or parenchymal lung disease) in which case first-line chemotherapy is appropriate
References
- ↑ Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344 (11):783-92. DOI:10.1056/NEJM200103153441101 PMID: 11248153
- ↑ Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L et al. (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20 (3):719-26. PMID: 11821453
- ↑ Alvarez RH, Guarneri V, Icli F, Johnston S, Khayat D, Loibl S et al. (2011) Bevacizumab Treatment for Advanced Breast Cancer. Oncologist ():. DOI:10.1634/theoncologist.2011-0113 PMID: 21976315
- ↑ Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N (2005) Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Mol Cell Endocrinol 239 (1-2):27-36. DOI:10.1016/j.mce.2005.04.008 PMID: 15950373