Abstract PS5-03-30: Neoadjuvant Chemo-Immunotherapy Yields Survival Comparable to Upfront Surgery in Metaplastic Breast Cancer: A National Cancer Database Analysis

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Abstract Purpose: Metaplastic breast carcinoma (MpBC) is a rare and aggressive subtype of breast cancer, oftencharacterized by triple-negative (TN) receptor status and a limited response to standardchemotherapy. The optimal treatment strategy remains undefined. This study evaluates overallsurvival (OS) in patients with TN-MpBC treated with neoadjuvant chemotherapy (NAC) orneoadjuvant chemo-immunotherapy (NACIO) compared to upfront surgery using the NationalCancer Database (NCDB). Methods:A retrospective cohort analysis was conducted using the NCDB to identify patients diagnosedwith stage I-III TN-MpBC between 2010 and 2022 treated with NAC, NACIO, or upfront surgery. Primary endpoints included overall survival (OS), pathologic complete response (pCR),and breast conservation rates. Breast conservation and pathologic complete response wereanalyzed using logistic regression, and overall survival was analyzed using Cox proportionalhazard model. Results: Of 4,953 patients, 3429 (69.2%) underwent upfront surgery, 1232 (24.9%) received NAC, and292 (5.8%) received NACIO. No significant difference in OS was observed between NACIOand surgery-first approaches (HR = 0.80, 95% CI: 0.51-1.27; p = 0.3), but NAC was associatedwith a 37% increased risk of mortality compared to upfront surgery (HR = 1.37, 95% CI: 1.21-1.56; p < 0.001 NACIO was associated with a 62% higher likelihood of achieving pCRcompared to NAC (OR = 1.62, 95% CI: 1.11-2.38; p = 0.013). The rate of breast conservationwas not significantly different between NACIO and upfront surgery (OR = 0.8, 95% CI: 0.61-1.05; p = 0.11), but patients receiving NAC were 27% less likely to undergo breast-conservingsurgery compared to those undergoing surgery first (OR - 0.73, 95% CI: 0.63-0.84; p < 0.001). Conclusion: In patients with TN-MpBC, NACIO demonstrated comparable survival outcomes to upfrontsurgery and improved pCR rates compared to NAC. These findings suggest that integratingimmunotherapy into neoadjuvant treatment may offer clinical benefit, warranting furtherprospective investigation. Citation Format: M. Nelis, A. Chichura, L. Zhang, V. Gadi. Neoadjuvant Chemo-Immunotherapy Yields Survival Comparable to Upfront Surgery in Metaplastic Breast Cancer: A National Cancer Database Analysis [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 PS5-03-30.

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