Abstract
BACKGROUNDS: Neoadjuvant therapy (NAT) is a cornerstone in the management of breast cancer (BC), enabling tumor downstaging and improved surgical options. METHODS: This study retrospectively analyzed 607 BC patients treated with NAT and surgery at IRCCS Humanitas Research Hospital, Milan, Italy, to compare long-term oncologic outcomes of breast-conserving surgery (BCS) versus mastectomy. Patient demographics, tumor characteristics, and treatment details were analyzed using descriptive statistics, logistic regression, and Cox proportional hazards models. RESULTS: Of the 607 patients, 54.7% underwent BCS, and 45.3% had mastectomy. BCS was associated with significantly superior 10-year outcomes compared to mastectomy, including disease-free survival (DFS, 75.2% vs. 71.1%, p = 0.001), distant DFS (75.2% vs. 71.1%, p = 0.001), overall survival (OS, 82.9% vs. 78.1%, p = 0.002), and BC-specific survival (BCSS, 87.7% vs. 83.1%, p = 0.001). Pathologic complete response (pCR) emerged as a protective factor across all endpoints, while mastectomy was independently associated with worse BCSS (HR: 2.068, 95% CI: 1.016-4.210, p = 0.045). CONCLUSIONS: Our findings demonstrate the oncologic safety and potential superiority of BCS over mastectomy in NAT-treated BC patients, highlighting the importance of individualized surgical decision-making to optimize survival outcomes.