Principles and indications of endocrine treatment of advanced breast cancer

Abstract

The numerous trials that have been conducted in advanced breast cancer in premenopausal and postmenopausal women have increased the empiric basis for systemic cytotoxic and endocrine treatment. The treatment results have improved but are still very unsatisfactory, and with all the drugs now at our disposal many questions are still unanswered. For instant this applies to the optimal composition and scheduling of endocrine treatment, cytotoxic treatment, and combinations of these two treatments. During recent years the results of experimental studies have expanded our knowledge of the biology of breast cancer. Future clinical trials should be designed to test and use this information gained from basic research with the aim of improving the rational basis of treatment and obtaining better treatment results in advanced breast cancer.

PIP: This paper summarizes the available data on the efficacy of endocrine and cytotoxic therapy for breast cancer in pre- and postmenopausal women. Various studies which were conducted suggested that regardless of hormone receptor status, premenopausal women should receive combined endocrine and cytotoxic therapy. However, it is now believed that future trials should take into account hormone receport status. For ER+ tumors, the standard initial treatment should be ovariectomy and later tamoxifen and chemotherapy could be added. A table, included in this brief review, summarizes treatment strategy for premenopausal women. If ER status is unknown treatment should include ovariectomy and combination chemotherapy; if ER+, ovariectomy along with tamoxifen and chemotherapy if indicated; and if ER-, then only combination chemotherapy. To a great extent, antiestrogens have been substituted in the treatment of breast cancer in postmenopausal women. Estrogens have been administered most widely and induce up to a 30% response; trials with antiestrogens have obtained similar results and thus tamoxifen is being used widely. Also it appears that the effect of treatment is related to the presence of estrogen receptors in the tumor tissue and thus 50-70% of ER+ tumors will respond to estrogens or antiestrogens. Tamoxifen apears to have a lower frequency and milder degree of side effects. Multi-drug therapy has now superseded single drug treatment in the last 5-10 years. If ER status in postmenopausal patients is unknown, the 1st treatment should be chemotherapy for women under age 60-70 and endocrine therapy for the 2nd treatment. In women older than 60-70, the preferred 1st choice therapy should be endocrine. For premenopausal women, those with ER+ tumors, endocrine therapy with tamoxifen should be the therapy of choice; in those with ER- tumors, chemotherapy should be the lst treatment.