Abstract PS4-08-09: Long-term outcomes and prognostic factors in metaplastic breast cancer treated with curative intent: a 22-year multicenter retrospective cohort study

Abstract Background: Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer with limited guidance on an optimal management approach in existing clinical guidelines. We evaluated long-term outcomes and treatment efficacy in early MpBC patients across major cancer centers in Hong Kong. Methods: Women with non-metastatic MpBC diagnosed from January 2001 to December 2023 at four Hong Kong hospitals were identified via Hong Kong Cancer Registry. Clinical data, treatment response, recurrence, and survival were analyzed by histological and molecular subtype according to current standards, based on review of original pathology reports. Survival analyses were conducted using the Kaplan-Meier method and compared using log-rank test. Factors associated with survival were evaluated by univariate and multivariate Cox regression. Results: In total, 145 consecutive patients with non-metastatic MpBC were included. The median age at diagnosis was 57 years (IQR 51-68 years), with 64.8% being postmenopausal. Most patients presented with a solitary tumor (94.5%), commonly in upper outer quadrant (58.6%). Squamous cell carcinoma (20.7%) and spindle cell carcinoma (13.1%) were the most common histological subtypes. Most cases were stage II (55.2%), with a median tumor size of 3.5 cm (IQR 2.4-6.0 cm), node-negative at diagnosis (66.2%), and grade 3 tumors (66.9%). Molecular subtyping showed that 49.7% of tumors were triple-negative, 45.5% were hormone receptor-positive only (≥1% ER and/or PR-positive tumor cells), 2.8% were HER2-positive only, and 2.1% were both ER/PR-positive and HER2-positive. 4.1% of tumors were ER low, and 37.9% HER2 low. Most patients underwent mastectomy (77.2%) with axillary dissection (58.6%), and 93.8% achieved clear margins. Neoadjuvant chemotherapy was given to 13.8% of patients, with a pathological complete response (pCR) in 5.0% and a partial response in 50.0%. Adjuvant chemotherapy and radiotherapy were given to 57.2% and 60.7% of patients, respectively. At a median follow-up of 112 months (IQR 28-165), the 5-year overall survival was 67%. Five-year locoregional and distant relapse-free survival rates were 90.4% and 72.1%, respectively. Locoregional recurrence occurred in 11%, and distant metastases in 27.6% of patients, mainly involving visceral sites (90%). Upon univariate analysis followed by multivariate analysis adjusted for grade, T stage, and molecular subtype, adjuvant chemotherapy was significantly associated with improved overall survival (HR 0.42, 95% CI 0.22-0.82, p=0.01), while adjuvant radiotherapy was not (HR 0.69, 95% CI 0.38-1.24, p=0.21). In T3/4 or node-positive subgroup, adjuvant chemotherapy remained significantly associated with improved overall survival (HR 0.32, 95% CI 0.12-0.83, p=0.02), whereas adjuvant radiotherapy did not show significance for overall survival (HR 0.65, 95% CI 0.29-1.45, p=0.29) or for locoregional relapse-free survival (HR 0.98, 95% CI 0.40-2.40, p=0.96). No significant differences in pCR rates following neoadjuvant chemotherapy were observed across molecular subtypes (p=0.67). Adjuvant endocrine therapy was not associated with overall survival in hormone receptor-positive cases (p=0.88), nor was targeted therapy in HER2-positive cases (p=0.47). Conclusion: This study showed that MpBC is a distinct subtype of breast cancer, characterized by unique clinicopathological characteristics and responsiveness to treatments. Adjuvant chemotherapy was associated with improved overall survival in non-metastatic MpBC, while adjuvant radiotherapy did not demonstrate a significant benefit. The low response rate to neoadjuvant chemotherapy highlights the urgent need to develop novel therapeutic strategies to enhance outcomes for this challenging patient population. Citation Format: S. S. Tse, K. Bao, K. Cheung, J. Chow, I. Wong, C. Wong, O. Mang, H. Yiu, C. Kwan. Long-term outcomes and prognostic factors in metaplastic breast cancer treated with curative intent: a 22-year multicenter retrospective cohort 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 PS4-08-09.