Abstract PS4-10-07: Pathologic complete response rates in early-stage triple negative metaplastic breast cancer in the neoadjuvant immunotherapy era: a retrospective review

Abstract Introduction: Metaplastic breast cancer (MpBC) is a rare and histologically diverse subtype of breast cancer (BC) that is frequently triple negative (TN) and exhibits poor responsiveness to chemotherapy (CT). Our group previously reported a low pathologic complete response (pCR) rate among patients (pts) with MpBC treated with neoadjuvant CT in the pre-immunotherapy (IO) era. The standard neoadjuvant approach for pts with stage 2-3 TNBC has evolved with the results of the KEYNOTE-522 (KN522) trial, which demonstrated improved pCR rates, event-free survival (EFS), and overall survival (OS) with the addition of pembrolizumab to CT. However, pts with MpBC were not well-represented in KN522, and their response to IO remains poorly characterized. In this study, we examine the pCR rate with the addition of IO to neoadjuvant CT in pts with TN MpBC. Methods: Pts diagnosed with MpBC and treated at Miami Cancer Institute between 2017-2024 were retrospectively identified by COTA real-world Analytics® platform following IRB approval. Eligible pts had stage 2-3 ER-negative (defined as ER 10%), PR-negative, HER2-negative MpBC, received neoadjuvant systemic therapy, and subsequently underwent definitive surgery. Demographic, clinical, treatment and outcome data were extracted from the electronic health record. pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes at the time of surgery. Kaplan-Meier method was used to estimate median disease-free survival (mDFS) and median OS (mOS). Comparison between treatment groups for pCR were performed using Fisher’s exact test. No multivariable or survival modeling was performed due to limited statistical power in this small cohort. All p values were two-sided. Results: A total of 27 pts were included in the analysis; 16 pts received CT (in the pre-IO era) with 19.2 months (m) median follow up and 11 pts received CT + IO with 15.5m median follow up. Spindle cell histology was reported in 18.5% of tumors, non-spindle cell in 59.3% and 22.2% were not further specified. Most patients (81.5%) had clinical stage 2 disease, 18.5% had stage 3; median tumor size was 3.2 cm. Anthracycline-based CT was administered to 81.5% of pts, and the remainder received non-anthracycline regimens. pCR was achieved in none of the 16 pts (0.0%) who received CT alone and in 3 of 11 pts (27.3%) who received CT + IO (p=0.046). Among the 3 pts who achieved pCR, 2 had non-spindle cell histology and 1 unspecified. All 3 pCR pts had stage 2 disease, received IO and anthracycline, and experienced immune-related adverse events. mDFS was 23.9m in the CT group and 14.6 m in the CT + IO group (p = 0.641), though follow-up duration differed between groups. Among all pts, mDFS was 15.3 m in those who did not achieve pCR and was not reached in those that did (p = 0.226). mOS was not reached in the CT group and was 20.7m in the CT + IO group (p = 0.192). Conclusion: In this small, retrospective real-world analysis of pts with early-stage TN MpBC, the addition of IO to neoadjuvant CT was associated with a higher pCR rate compared to CT alone. Although the observed pCR rate of 27.3% with CT+IO is lower than that reported in KN522 for unselected TNBC, this likely reflects the small sample size and the inherently CT-resistant biology of MpBC. None of the pts in the CT alone group achieved pCR, suggesting that IO may help to overcome CT resistance in MpBC. Differences in mDFS and mOS were not statistically significant, possibly due to limited follow up and sample size. Despite these limitations, our findings highlight the importance of incorporating IO into treatment for MpBC. Future multicenter analyses are ongoing to validate these results in a larger, more diverse population and to further explore the role of histologic subtypes and immune biomarkers in predicting response. Citation Format: N. Dempsey, L. Hodgson, A. Sandoval-Leon, L. Carcas, M. Ahluwalia, C. Wang, H. Kim, P. Advani, R. Mahtani. Pathologic complete response rates in early-stage triple negative metaplastic breast cancer in the neoadjuvant immunotherapy era: a retrospective review 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 PS4-10-07.