Abstract PD7-11: Impact of neoadjuvant pembrolizumab on ovarian function in young patients with triple-negative breast cancer (TNBC): Longitudinal analysis from NeoSTOP and NeoPACT trials

Abstract Background: Neoadjuvant chemotherapy plus pembrolizumab (NACT+P) is standard of care for most patients with stage II-III TNBC. There is lack of clinical data on the ovarian toxicity of immune checkpoint inhibitors in patients with breast cancer. We utilized serial serum samples and data from two completed neoadjuvant trials, NeoSTOP (NACT: carboplatin + paclitaxel--AC or carboplatin + docetaxel) and NeoPACT (NACT+P: carboplatin + docetaxel + pembrolizumab) to compare ovarian toxicity of chemotherapy and chemoimmunotherapy. Methods: Patients 50 years of age and self-reported premenopausal enrolled in NeoSTOP (n=40) and NeoPACT (n=52) were identified, and those with available serum samples were included in the analysis (n=36 NeoSTOP, n=49 NeoPACT). Estradiol (E2), progesterone (PG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) were assessed at serial time points: pretreatment (pre-tx), post neoadjuvant treatment (pre-surgery), and 3-12 months and 12-24 months after completing all adjuvant chemotherapy. Assay-specific published cut points were used to categorize biochemical menopausal status. Results: Baseline characteristics including age, nodal status, race, and pretreatment AMH, E2, PG, FSH, and LH levels were similar in NACT and NACT+P groups. Pre-surgery time point showed significant decline in AMH, E2, and PG and increase in FSH and LH compared to pre-tx levels in both NACT and NACT+P groups. AMH pre-tx vs pre-surgery: median 116 pg/mL vs 1.3 pg/mL, p0.001; E2 pre-tx vs pre-surgery: 108 vs 21.3 pg/mL, p0.001; PG pre-tx vs pre-surgery: 1.36 vs 0.790 ng/mL, p0.001; FSH pre-tx vs pre-surgery: 2.71 vs 47.0 mIU/mL, p0.001; and LH pre-tx vs pre-surgery: 3.07 vs 24.8 mIU/mL, p0.001. At pre-surgery, 100% of patients in both NACT and NACT+P cohorts had postmenopausal AMH (10 pg/mL), p=1.000; 60% and 55% in NACT and NACT+P groups had postmenopausal E2 (≤30 pg/mL), p=0.817; 69% and 76% in NACT and NACT+P groups had postmenopausal FSH (20 mIU/mL), p=0.608; and 80% and 86% in NACT and NACT+P groups had postmenopausal LH (7 mIU/mL), p=0.553. Evaluation at 3-12 and 12-24 months post adjuvant chemotherapy demonstrated hormone recovery in a substantial proportion of patients in both groups. AMH recovered to non-postmenopausal range in 50% and 44% of patients in NACT and NACT+P groups, p=0.769. FSH recovered in 77% and 76% in NACT and NACT+P groups, p=1.000. E2 recovered to premenopausal range in 100% of patients in both the NACT and NACT+P groups, p=1.000. AMH was lower at 3-12 months post chemotherapy compared to pre-tx levels in both NACT (p=0.007) and NACT+P groups (p0.001). However, at 3-12 months there was no difference in AMH between NACT and NACT+P groups (p=0.379), indicating similar impact of NACT and NACT+P on ovarian reserve. 52% patients in the NACT group and 68% in the NACT+P group reported return of menstrual cycles during follow-up (p=0.214). Return of menstrual cycles was highly correlated with AMH recovery (p0.001). On multivariate analysis, only pre-tx AMH predicted AMH recovery (p=0.027). Conclusions: To our knowledge this is the first report on impact of pembrolizumab on ovarian function and recovery in young premenopausal patients with breast cancer. Our findings indicate that immediate post-NACT/NACT+P hormone levels are in the postmenopausal range in the majority of patients and thus are not reliable indicators of long-term ovarian toxicity. Longitudinal analysis shows biochemical hormone recovery in 44%-100% of patients depending on the hormone assessed. Similar rates of biochemical hormone recovery and menstrual recovery were noted with chemotherapy and chemoimmunotherapy, suggesting that pembrolizumab probably does not have an additive effect on ovarian toxicity. Citation Format: P. Sharma, R. Yoder, W. Cui, A. Winship, K. Hutt, S. Loi, Q. Khan, A. O'Dea, L. Nye, D. Satelli, J. Staley, R. Puri, A. Mitra, K.-A. Phillips, L. Alesi, Y. Lewis, J. O'Shaughnessy, H. Pathak, A. K. Godwin. Impact of neoadjuvant pembrolizumab on ovarian function in young patients with triple-negative breast cancer (TNBC): Longitudinal analysis from NeoSTOP and NeoPACT trials 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 PD7-11.