Impact of pembrolizumab on ovarian function in young triple negative breast cancer patients treated with chemo-immunotherapy

Purpose: Pembrolizumab plus neoadjuvant chemotherapy (P-CT) is the new standard in early-stage triple-negative breast cancers (TNBC). Pembrolizumab impact on ovarian reserve remained unknown . We evaluated the impact of pembrolizumab on ovarian reserve, through plasmatic Anti-M ü llerian (AMH) analysis, in young TNBC patients. Methods: TNBC patients £43 years treated by P-CT whose plasma samples were available before and after treatment were included retrospectively (P-CT group). AMH, FSH and oestradiol were analysed before and after treatment, then compared to a retrospective cohort treated with CT alone (No-P group). Results: P-CT patients (N=17) and No-P patients (N=67) had comparable median age, BMI, smoking exposure, BRCA status, oral hormonal contraceptive use and baseline AMH. One year after the start of treatment, AMH fell from 1.08 to 0.01 ng/mL (p<0.0001 vs baseline) and from 1.4 to 0.018 ng/mL (p<0.0001), in the P-CT and No-P groups, respectively. 9/17 P-CT patients, and 23/67 No-P patients, had undetectable AMH after treatment (p=0.3). FSH and oestradiol were comparable between the two groups, before and after treatment. Unlike the No-P group, no recovery of AMH was observed two years after treatment initiation in a limited sub-group of P-CT patients. Conclusion: No supplementary impact of pembrolizumab to CT on AMH evolution was observed. The absence of AMH partial recovery 2 years after treatment initiation warrants vigilance.