Comprehensive Clinicopathologic Evaluations of 149 Metaplastic Carcinomas of the Breast Treated With Neoadjuvant and Adjuvant Chemotherapy

Metaplastic breast cancer (MBC) is a rare subtype of breast cancer, and its clinical presentations and outcome are not clear. This multi-institutional study comprehensively evaluated the clinicopathologic features, treatment patterns, and outcomes of 149 MBC cases. In total, 149 MBC cases diagnosed from 2005 to 2023 were included and compared with 350 non-MBC triple-negative breast cancer (TNBC) cases diagnosed from 2004 to 2019: 62 MBCs and 174 TNBCs were treated with neoadjuvant chemotherapy (NACT) and 87 MBCs and 176 TNBCs with adjuvant chemotherapy (ACT). We evaluated pathologic variables, including necrosis, lymphovascular invasion, tumor-infiltrating lymphocytes (TILs), tumor nuclear grade, Nottingham grade, tumor size, the presence of ductal carcinoma in situ, and the presence and percentage of different metaplastic components. Clinical data, including age, race, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status, local recurrence-free survival, and metastasis-free survival (MFS), were retrieved. The median follow-up time was 58.9 months for all patients. Only 8.1% of patients with MBC (n = 5) achieved pathologic complete response (pCR) when treated with NACT compared with 37.9% of TNBC patients (P <. 0001). None of the patients with MBC who achieved pCR developed metastasis. No clinicopathologic variables were associated with the pCR rate in MBC. The proportion of metaplastic components was not associated with the pCR rate or MFS in MBC cases. Patients with MBC treated with NACT had significantly shorter MFS than those treated with ACT (P =. 011). In patients with MBC who did not achieve pCR after NACT, larger tumor size was associated with shorter MFS (P <. 001). In patients with MBC who received ACT, higher TILs level was associated with longer MFS (P =. 016). This study with large cohorts showed patients with MBC had a low pCR rate to NACT, and those patients who achieved pCR had excellent prognosis. Therefore, it is important to identify which patients benefit from NACT. The proportion of metaplastic component was not associated with the pCR rate or MFS, supporting the current recommendation that breast carcinoma with any metaplastic component should be diagnosed as MBC. Finally, higher TILs levels were associated with improved MFS in patients with MBC treated with ACT. Further investigation is warranted to define biomarkers and patient selection for NACT versus ACT in MBC.