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ABSTRACT
Endocrine therapy remains pivotal in the adjuvant therapy of premenopausal women with hormone receptor-positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that this technique is effective, perhaps because of the endocrine ablative effect of chemotherapy. Adjuvant trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy (cyclophosphamide, methotrexate, fluorouracil) suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors express estrogen and/or progesterone receptors. Endocrine therapy with ovarian ablation, tamoxifen, or the combination is also useful in the metastatic setting in premenopausal women.
Developed over a century ago,[ 1 ] endocrine therapy remains the most effective and the most clearly targeted form of systemic therapy for breast cancer. Endocrine treatments work best in women whose tumors are positive for estrogen receptors (ER) and/or progesterone receptors (PR). As we search for newer targeted therapies that will shrink cancers effectively with few undesired side effects and carry out complex statistical analyses to identify predictive factors, we should keep in mind the first targeted cancer therapy - ovarian ablation for breast cancer - and the first predictive factor for treatment of any cancer - the estrogen receptor. [2]
Adjuvant treatment for premenopausal women is an important current focus in the setting of breast cancer. In Canada, 20% of newly diagnosed breast cancer cases occur in patients under 50 years of age, 4% are in women under 40, and 1 % to 2% are in those under 35. [3] Of these, about half will have ER- and/or PR-positive disease.
Ovarian Ablation as Adjuvant Endocrine Therapy
For many years, adjuvant ovarian ablation was believed to be helpful in premenopausal women with breast cancer, but randomized trials were not done. A few small randomized trials were carried out in the 1960s and 1970s, but prior to the first Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Overview (aka the Oxford Overview) in 1984,[4] it was generally thought that these trials showed no benefit for ovarian ablation. This strategy therefore came to be considered an outmoded breast cancer therapy. When the meta-analytic techniques used in the EBCTCG Overview were applied to these small trials,...