Long-term safety of controlled ovarian stimulation for fertility preservation before chemotherapy treatment in patients with breast cancer

Abstract

Objective: To evaluate the long-term safety of controlled ovarian stimulation for fertility preservation before breast cancer chemotherapy treatment.

Design: Retrospective observational cohort.

Setting: Tertiary medical center.

Patient(s): Two hundred thirteen women aged 18 to 43 years with newly diagnosed stage I-III breast cancer treated with systemic chemotherapy during 2015-2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients, and 141 did not (controls).

Intervention(s): controlled ovarian stimulation for fertility preservation.

Main outcome measure(s): Invasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first.

Result(s): At diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs. 38.5 years), were less likely to be partnered (44.4% vs. 90.1%) or parous (38.9% vs. 95%), and were more likely to harbor a BRCA germline mutation (36.5% vs. 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being >5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls. Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. Five-year invasive disease-free survival was 80% for fertility preservation recipients and 86% for controls. In a multivariate analysis adjusted for statistically significant covariates, invasive disease-free survival remained similar between the groups (hazards ratio [HR], 0.86; 95% confidence interval [CI], 0.4-1.87). Invasive disease-free survival rates were not statistically different in clinically relevant subgroups, including patients receiving neoadjuvant chemotherapy (HR, 1.57; 95% CI, 0.62-3.99) and those cotreated with tamoxifen during stimulation because of an estrogen receptor positive disease (HR, 1.66; 95% CI, 0.67-3.49).

Conclusion(s): Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emergent clinically relevant subgroups.

Keywords: Fertility preservation; breast cancer; controlled ovarian stimulation; neoadjuvant chemotherapy; tamoxifen.