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-Müllerian (AMH) analysis, in young TNBC patients.

Methods: TNBC patients < 43 years treated by P-CT (carboplatin/paclitaxel/epirubicin/cyclophosphamide plus pembrolizumab) of which plasma samples were available before and after treatment were included retrospectively (P-CT group). AMH, FSH, and estradiol were analyzed before and after treatment, then compared to a retrospective cohort of TNBC patients treated with chemotherapy alone (cyclophosphamide/anthracycline/taxanes) (No-P group).

Results: P-CT patients (N = 17) and No-P patients (N = 62) had comparable median age, BMI, smoking exposure, BRCA status, oral hormonal contraceptive use at diagnosis, and baseline AMH. Drugs used were comparable in both groups, except for carboplatin and pembrolizumab, only used in P-CT group. One year after the start of treatment, AMH fell from 1.08 to 0.01 ng/mL (p = 0.0001) and from 1.39 to 0.018 ng/mL (p < 0.0001), in the P-CT and No-P groups, respectively, without difference according to pembrolizumab exposure (p = 0.25). 9/17 P-CT patients (53%), and 21/62 No-P patients (34%), had undetectable AMH after treatment (p = 0.25). FSH and estradiol were comparable between the two groups, before and after treatment.

Conclusion: No additional impact of pembrolizumab versus chemotherapy alone on AMH evolution was observed in TNBC patients < 43 years. Nevertheless, undetectable AMH 1 year after the start of treatment was common in the P-CT group. Larger studies are essential to confirm these preliminary results and assess long-term impact of pembrolizumab on ovarian reserve.