Abstract RF2-06: Impact of Immune Checkpoint Inhibition (CPI) on Fertility in Young Women with Early Triple-Negative Breast Cancer (TNBC) receiving neoadjuvant Chemotherapy (NACT): A Prospective Substudy of the NSABP B-59/GBG-96-GeparDouze Trial

Abstract Introduction NACT is associated with a high risk of ovarian failure in premenopausal women with breast cancer. The impact of CPI added to NACT on chemotherapy-induced ovarian failure (CIOF) remains underexplored. This study analyses the effects of combined NACT and CPI on ovarian function, assessed through different hormonal parameters in patients (pts) with TNBC. Methods This prospective, substudy included women aged≤45 years (yrs) without history of hysterectomy and/or ovarectomy enrolled within this trial (SABCS2024). Pts received anthracycline, cyclophosphamide, taxane and carboplatin containing NACT with atezolizumab (CTA) or without (CT). The main objective was to assess the rate of CIOF, defined as postmenopausal levels of follicle-stimulating hormone (FSH>25.8 IU/l) and Estradiol (E2<5 pg/ml), further objectives were the assessment of Anti-Mullerian Hormone (AMH), and amenorrhea rate. Blood samples were prospectively collected at baseline (BL), at end of therapy (EOT), and at 6, 12, 18 and 24 months (mo) after EOT. E2 (pg/ml), FSH (IU/l), and AMH (ng/ml) were centrally assessed. Pts had to have at least a BL sample and one additional sample collected at one of the other time points to be evaluable. Results A total of 173 pts were included in the ovarian substudy across 85 centres in Germany and Spain. 133 pts (CT n=63; CTA n=70) had blood samples taken on at least two time points. The median age at BL was 37 yrs (range 33-41 yrs, 35%≥40 yrs), the median BMI was 24 kg/m2, 12%≥30 kg/m2. The E2 levels (Table) decreased during therapy but increased after EOT. In both arms E2 levels recovered 24 mo after EOT with median E2 levels of 53.3 in CTA vs 81.6 in CT (p=0.348). In both arms E2 did not reach baseline values. Increase in median FSH levels after EOT was observed over time and remained postmenopausal in the CPI group after 24 mo. 34.2% pts experienced CIOF at EOT (CTA: 40.6%, CT: 26.8%; p=0.13), and overall, 10% had persistent CIOF 24 mo after EOT; which was higher when CPI was added (CTA 7.5%; CT 2.5%; p=0.06, Table). At BL, AMH<0.22, suggestive of impaired fertility, was observed in only a minority of pts (8.6% CTA, 12.7% CT) but in all pts at EOT. After 24 months, recovered AMH≥0.22 was measured in 27.5% (CTA) and 25% (CT) of pts (Table). Conclusion This first prospective study investigating the influence of CPI on ovarian failure. Two years after treatment 10% had permanent CIOF after receiving NACT for TNBC. Pts with CPI tended to have higher rates of CIOF at all timepoints and fewer pts had an ovarian function recovery supporting the biological theory that CPI on top of chemotherapy influence fertility. Our results contribute to understanding CPI's impact on fertility in young pts receiving carboplatin containing NACT with CPI for early TNBC and provide valuable insights for fertility counselling. Citation Format: M. Reinisch, A. Schneeweiss, V. Schaser, C. Solbach, C. Denkert, P. Rastogi, F. Moreno, T. Freeman, T. Link, J. Mouta, S. Seiler, R. Mey, Á. Rodríguez Lescure, V. Bjelic-Radisic, P. A. Fasching, M. Balic, M. Untch, K. Rhiem, K. Lüdtke-Heckenkamp, J. Huober, S. Morales, I. Blancas, J. Holtschmidt, V. Nekljudova, N. Wolmark, C. E. Geyer, S. Loibl. Impact of Immune Checkpoint Inhibition (CPI) on Fertility in Young Women with Early Triple-Negative Breast Cancer (TNBC) receiving neoadjuvant Chemotherapy (NACT): A Prospective Substudy of the NSABP B-59/GBG-96-GeparDouze Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF2-06.