Adjuvant endocrine therapy for premenopausal women: risk stratification, type and duration

Abstract

Updated results from the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) have helped to identify differential value of various adjuvant endocrine therapy strategies in high-risk and low-risk premenopausal early breast cancer. With a median follow-up of 8 years in SOFT, there is now a significant improvement in disease-free survival (DFS) for those assigned to receive 5 years of tamoxifen plus ovarian function suppression (T + OFS) as compared with tamoxifen (T). Further improvement in DFS was observed for those assigned exemestane plus OFS (E + OFS). While the relative treatment effect from the addition of OFS to tamoxifen in the no chemotherapy and prior chemotherapy cohorts in SOFT was similar, larger absolute improvement in DFS was observed with endocrine therapy escalation in the premenopausal cohort who had received chemotherapy. Despite some improvement in DFS in the lower risk no-chemotherapy cohort, the 8-year results for that cohort continue to show a low risk of distant metastases with the use of adjuvant tamoxifen as sole systemic therapy. A small overall survival advantage from the addition of OFS to tamoxifen has now emerged in SOFT, which appears more clinically meaningful in the prior chemotherapy cohort.In the joint analysis of SOFT and TEXT, there is currently no overall survival improvement at 8 years for those assigned E + OFS versus T + OFS, despite a significant reduction in distance recurrences with E + OFS. Assessing absolute improvements in freedom from distant recurrence observed with the different endocrine strategies across the risk spectrum of patients with HER2-negative tumours in SOFT and TEXT, may assist decision-making for premenopausal patients.