Controversies in adjuvant endocrine treatment of premenopausal women

For patients with hormone receptor-positive breast cancer, some form of endocrine therapy is central to the management of their disease. For premenopausal patients in whom estrogen synthesis occurs primarily in the ovaries, current treatment options include ovarian ablation or suppression and selective estrogen receptor modulators such as tamoxifen and toremifene. Ovarian ablation and tamoxifen have demonstrated their effectiveness in the adjuvant setting, reducing the risk of recurrence and death. However, although some studies suggest ovarian ablation results in an equivalent outcome to chemotherapy alone, studies examining the combination have not demonstrated a clear benefit with the addition of ovarian suppression to standard chemotherapy. Results from trials combining ovarian suppression with tamoxifen have also been inconclusive. Finally, although aromatase inhibitors cannot be used as monotherapy in premenopausal patients, the reduction in the risk of recurrence observed with the integration of these agents into adjuvant regimens in postmenopausal patients when compared with the standard 5 years of tamoxifen has stimulated interest in evaluating the combination of ovarian suppression with an aromatase inhibitor in premenopausal women. Several ongoing trials will investigate these combinations as well as ovarian suppression plus tamoxifen.