Adjuvant hormonal therapy for premenopausal women with breast cancer

Hormonal manipulation has been used for over 100 years to treat breast cancer. Ovarian ablation/suppression and tamoxifen are currently accepted adjuvant endocrine therapies for premenopausal breast cancer. Methods of permanently ablating ovarian function include surgical oophorectomy and radiation-induced ovarian failure; medical castration with luteinizing hormone-releasing hormone analogues is a reversible approach. Adjuvant chemotherapy frequently results in permanent amenorrhea and thus represents an indirect form of ovarian ablation. Although early randomized trials of ovarian ablation suffered from small sample sizes and design flaws, a meta-analysis of their results through the Early Breast Cancer Trialists' Collaborative Group demonstrated a clear benefit from ovarian ablation as a single intervention in the adjuvant treatment of women less than 50 years of age with breast cancer. The Early Breast Cancer Trialists' Collaborative Group meta-analysis also demonstrated the efficacy of 5 years of adjuvant tamoxifen as a single treatment modality, regardless of age. Even with these improvements in disease-free and overall survival, several important questions remain unanswered. The relative efficacy of adjuvant chemotherapy versus ovarian ablation/suppression has not been strictly defined. However, the data suggest that the clinical benefit of either chemotherapy or ovarian ablation/suppression and 5 years of tamoxifen is similar. Thus, ovarian ablation/suppression combined with tamoxifen is a reasonable alternative to chemotherapy for some women with good-risk early-stage breast cancer (high hormone receptor expression, low-grade or lymph node-negative disease), particularly those wishing to preserve fertility. The value of combining ovarian ablation/suppression with chemotherapy, other endocrine therapy, or both and ameliorating the long-term morbidity of estrogen deprivation remain important areas for investigation. With the advent of multiple targeted endocrine therapies with distinct mechanisms of action, there is a unique opportunity to design highly informative clinical trials that can define the optimal combinations and sequencing of hormonal therapies in the treatment of early-stage breast cancer.