Patterns of response of breast cancer after neoadjuvant chemotherapy according to molecular subtype

Neoadjuvant chemotherapy (NACT) is a key component in the treatment of locally advanced breast cancer, with pathologic complete response (pCR) varying by molecular subtype. This study evaluates pCR rates following NACT in a Lebanese cohort, stratified by molecular and clinicopathological features.Methods: This retrospective cohort included 187 women with stage T1-T4, N1, M0 breast cancer treated at the American University of Beirut Medical Center between 2010 and 2016. Molecular subtypes (Luminal A, Luminal B, HER2-positive, triple-negative) were determined by immunohistochemistry and/or FISH. pCR was defined as ypT0N0. Univariate and multivariate analyses were performed to identify predictors of pCR.Results: The median age was 45 years. Molecular subtype distribution was: Luminal A (28.9%), Luminal B (45.5%), HER2-positive (11.8%), and triple-negative (13.9%). Overall pCR was achieved in 12.8% (24/187) of patients. pCR rates significantly differed across molecular subtypes: HER2-enriched 45.5%, Luminal B 11.8%, triple-negative 11.5%, and Luminal A 1.9% (p = 0.005). Axillary involvement was also significantly associated with pCR (p < 0.001), while clinical T stage, tumor grade, focality/centricity, and chemotherapy regimen showed no significant associations. In multivariable logistic regression, molecular subtype remained an independent predictor of pCR (p = 0.002).

pCR rates varied markedly among molecular subtypes, being highest in HER2-enriched tumors and lowest in Luminal A. These findings support molecular subtype as a key determinant of treatment response and highlight its role in guiding neoadjuvant treatment strategies.