Hormonal factors predictive of fertility in patients with breast cancer interrupting adjuvant endocrine therapy to attempt pregnancy in POSITIVE trial

Abstract

Purpose The POSITIVE trial showed that premenopausal women with breast cancer (BC) can safely pause adjuvant endocrine treatment (ET) to attempt conception. 74 % of patients conceived spontaneously or through assisted reproductive technology (ART); Investigating hormonal factors that predict fertility was a key secondary endpoint. Methods Hormonal factors were assessed in non-pregnant women at months 3, 6, and 12 after ET interruption. The frequency of low ovarian reserve, defined as anti-Mullerian hormone (AMH) < 0.5 ng/mL at month 3, and of premature ovarian insufficiency (POI), defined as follicle stimulating hormone (FSH) > 25 IU/L at month 12, were primary measures. Secondary analyses to predict pregnancy included AMH, FSH, thyroid stimulating hormone (TSH), prolactin and ovulatory status (defined as progesterone >3 ng/mL at month 6), considering covariates such as age, treatment, and ART use. Results Of 518 women enrolled in POSITIVE, 438 were eligible for low ovarian reserve analysis. Low ovarian reserve was observed in 209 women (47.7 %), more frequently among older women and those with prior chemotherapy, but not in relation to ET type or duration. Overall, low ovarian reserve was associated with reduced odds of pregnancy (OR:0.52; 95 % CI:0.31–0.87). Of 142 patients evaluated for POI, 16.7 % of those who received prior chemotherapy experienced POI. FSH at month 3 was associated with POI, but only modestly with spontaneous pregnancy (OR:0.96; 95 %CI: 0.93–1.00); other factors were not predictive of pregnancy. Conclusion Hormonal factors are associated with pregnancy in BC patients pausing adjuvant ET to conceive, and their assessment may help to optimize fertility counseling. Trial registration ClinicalTrials.gov number NCT02308085.