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. 2025 Jul;212(1):79-86.
doi: 10.1007/s10549-025-07702-w. Epub 2025 Apr 22.

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

Affiliations

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

Anne Perdrix et al. Breast Cancer Res Treat. 2025 Jul.

Abstract

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.

Keywords: AMH; Early-stage triple-negative breast cancer; Immune checkpoint inhibitor; Ovarian reserve; Pembrolizumab.

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Conflict of interest statement

Declarations. Competing interests: FC has received honoraria and/or travel grants from Astra Zeneca, Daiichi, Gilead, MSD, Merck Serono, Nutricia, Novartis outside the submitted work. ML has received payment of congress fees from Daiichi, Lilly, MSD, Pfizer, GSK, Novartis, Mundi pharma, EISAI; and has undertaken consultancy for MSD, Astra-Zeneca, Pierre Fabre, GSK, Lilly and Seagen outside the submitted work. NO has received payment of congress fees from Pfizer, Gillead and Lilly; and has undertaken consultancy for Gilead and Astra Zeneca outside the submitted work. The other authors report no potential conflicts of interest. Ethical approval: The present study follows the French reference methodology MR-004 and was approved by the Institutional Scientific and Ethics Committees of Henri Becquerel Center (registering order N°2406B). Consent to participate: All patients signed a consent form allowing the conservation and use of their biological samples. No patient objected to the use of the anonymous data generated for research purposes, according to MR-004 methodology. Consent to publish: This manuscript does not contain any individual personal data.

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