Abstract PS3-11-25: Adjuvant ovarian function suppression (OFS) in HR+/HER2+ premenopausal breast cancer (BC) patients with pathologic complete response (pCR) or residual disease (RD) after neoadjuvant chemotherapy (NAC): a real-world study

Abstract Background: The HERA trial demonstrated survival benefits with the addition of OFS to adjuvant endocrine therapy (ET) in premenopausal patients (pts) with HR+/HER2+ early BC. However, the benefit of OFS over tamoxifen (TAM) alone remains unclear in the post-NAC setting, particularly among pts who achieve pCR or have RD. We present real-world survival outcomes comparing OFS-based ET vs. TAM alone in this specific population following NAC. Methods: We conducted a retrospective study of premenopausal pts ≤50 years with HR+/HER2+ BC who achieved pCR (ypTis/T0 ypN0) or had RD after NAC at Memorial Sloan Kettering (2008-2025). Pts were categorized by adjuvant ET: OFS+TAM or aromatase inhibitor (AI) vs. TAM alone. Pts receiving >1 ET type were classified according to the therapy received for >75% of their total ET duration. Primary endpoints were disease-free survival (DFS) and overall survival (OS), estimated using the Kaplan-Meier method and compared across ET groups using log-rank tests. Pt and treatment characteristics were compared between ET groups using chi-squared tests. Multivariable Cox proportional hazards models were used to evaluate associations between adjuvant ET and survival outcomes, adjusting for pathologic stage and adjuvant HER2 therapy. ET exposure was modeled as a time-dependent covariate to account for differences in exposure time among pts receiving >1 ET type. Results: A total of 309 pts were included: 157 with pCR and 152 with RD. Overall, 146 (47%) received OFS+TAM/AI and 163 (53%) received TAM alone. Median follow-up was 55.6 months (IQR 37-80). AC-THP was the primary NAC regimen (69%) in both ET groups. Compared to TAM alone, pts treated with OFS+TAM/AI were more likely to have clinical node-positive disease at baseline (63% vs. 51%, p=0.032) and to receive T-DM1 as adjuvant HER2-targeted therapy (36% vs. 15%, p<0.001). Five-year DFS was 89% with OFS+TAM/AI vs. 84% with TAM (p=0.12). No significant difference in OS was observed (p=0.20). In the full cohort, TAM was associated with inferior DFS compared to OFS+TAM/AI in multivariable analysis (HR 1.90; 95% CI, 0.91-3.98; p=0.088), with borderline statistical significance. Pathologic stage and adjuvant HER2-targeted therapy were significantly associated with DFS: stage III vs. pCR (HR 7.52; 95% CI, 2.83-20.0; p<0.001), and trastuzumab alone vs. T-DM1 (HR 3.60; 95% CI, 1.27-10.3; p=0.016). These results were consistent when analyzing the pCR and RD subgroups separately. In the pCR cohort, TAM showed a nonsignificant trend toward inferior DFS (HR 3.46; 95% CI, 0.72-16.6; p=0.12), while clinical stage III was associated with worse DFS (HR 4.67; 95% CI, 1.33-16.5; p=0.016). In the RD cohort, pathologic stage III (HR 4.09; 95% CI, 1.71-9.79; p=0.002) and trastuzumab monotherapy (HR 3.47; 95% CI, 1.16-10.4; p=0.026) were associated with worse DFS. TAM also showed a nonsignificant trend toward inferior DFS (HR 1.55; 95% CI, 0.65-3.67; p=0.30). Conclusions: In this real-world cohort of premenopausal pts with HR+/HER2+ BC who achieved pCR or had RD after NAC, OFS-based ET was more frequently prescribed to those with higher-risk features, such as clinical node-positive disease. Although this retrospective study was underpowered to detect definitive differences in DFS between ET strategies, a trend toward improved DFS was observed in pts treated with OFS+TAM/AI compared to TAM alone, independent of pathologic stage and adjuvant HER2-targeted therapy, with borderline statistical significance. These findings support the need for larger retrospective cohorts to better clarify the role of OFS for HR+/HER2+ BC in the post-NAC setting. Citation Format: D. Audi Blotta, N. Mai, M. Bromberg, Y. Chen, F. Parvin-Nejad, G. Plitas, P. Razavi, M. Robson, S. Modi. Adjuvant ovarian function suppression (OFS) in HR+/HER2+ premenopausal breast cancer (BC) patients with pathologic complete response (pCR) or residual disease (RD) after neoadjuvant chemotherapy (NAC): a real-world study [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 PS3-11-25.