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

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.