Ovarian Suppression for Breast Cancer: An Effective Treatment in Search of a Home

Abstract

Adjuvant endocrine therapy is the most important systemic treatment for the majority of women with hormone receptor–positive breast cancer. Our understanding of the role of endocrine therapy in premenopausal women has lagged considerably in comparison with our knowledge of its role in postmenopausal women. Tamoxifen, for example, was initially shown to be beneficial in postmenopausal women; only after many years were similar benefits demonstrated in premenopausal women. 1 In the last few years, adjuvant endocrine therapy for postmenopausal women has taken another step forward with the incorporation of the aromatase inhibitors into the treatment armamentarium. 2 The benefits seen with aromatase inhibitors, which arise as a consequence of estrogen deprivation, have contributed to continued interest in the use of ovarian suppression in premenopausal women. Why do we know so much less about endocrine therapy in premenopausal than in postmenopausal women? There are at least three reasons. First, breast cancer, and specifically hormone receptor–positive breast cancer, is much less common in premenopausal women than in postmenopausal women. However, receptor-positive breast cancer in premenopausal women is hardly a rare disease. There are approximately 47,000 cases of breast cancer in women younger than 50 years diagnosed in the United States each year; of these, 11,500 cases are in women younger than 40 years. 3 More than half of all premenopausal women with breast cancer have receptor-positive disease, resulting in more than 25,000 cases of receptorpositive disease among premenopausal women. Taking a more global perspective, there are hundreds of thousands of premenopausal women diagnosed each year with hormone receptor–positive disease. Second, there has been a longstanding conviction that chemotherapy was the more important treatment for younger women, and, consequently, trials of endocrine agents have been viewed as second-tier. There has been increasing reason to question this view, but translating hypotheses into practice-changing clinical trials can take many years. Finally, our understanding of endocrine therapy in premenopausal women has been clouded by the indirect endocrine effect of chemotherapy. At least some, if not most, of the benefit of chemotherapy in many premenopausal women with receptor-positive disease probably arises from suppression of ovarian function. There are several reasons to investigate new and im