Ovarian reserve as a measure of adjuvant chemotherapy benefit in HR+, HER2-, node-positive breast cancer: post hoc analysis of RxPONDER

The multicenter phase 3 RxPONDER trial compared endocrine therapy (ET) alone or with chemotherapy (CET) in patients with HR-positive, HER2-negative, node-positive breast cancer with recurrence score (RS) ≤ 25. CET benefit for the primary outcome, invasive disease-free survival (IDFS) was limited to premenopausal women who largely did not receive ovarian function suppression. Post hoc analysis of RxPONDER assessed hormones associated with ovarian reserve to further refine the prediction of CET benefit. Baseline estradiol, progesteroine, luteinizing hormone, and follicule-stimulating hormone were not predictive for CET benefit. Anti-Müllerian hormone (AMH) ≥ 10 pg/ml showed significant interaction with chemotherapy benefit for IDFS (p=0.0034). In the 64% if women with AMH ≥ 10 pg/ml (cutoff for normal ovarian reserve) IDFS was superior with CET compared with ET alone (HR 0.46; 95% CI 0.33-0.65), whereas CET was not beneficial in the 34% with low ovarian reserve (1.27; 0.81-1.99). Distant recurrence-free survival showed a similar pattern of results for AMH. Ultrasensitive inhibin B measured in the pg/ml range was also predictive of CET benefit. The authors conclude that among premenopausal patients aged < 55 years, participants with baseline AMH <10 pg/ml did not benefit from CET. Measures of ovarian reserve may refine selection of patients for CET.