Evaluating the Efficacy of Neoadjuvant Endocrine Therapy in HER2-Low Versus HER2-Negative Breast Cancer

HER2-low breast cancer has emerged as a distinct biological subtype with implications for treatment response. However, its impact on response to neoadjuvant endocrine therapy (NET) in hormone receptor-positive (HR+) breast cancer remains unclear. The objective of this study is to evaluate whether HER2-low status is associated with improved clinical response to NET among patients with early-stage HR+ breast cancer. A retrospective cohort study was conducted using data from the NCDB from 2010 to 2017, identifying women aged ≥ 18 years with stage I-III HR+ invasive breast cancer treated with NET, who had known HER2 immunohistochemistry status and response to NET documented. The primary outcome was clinical response to NET. We employed multivariable binomial logistic regression to examine how clinicopathologic factors influence the probability of any response to neoadjuvant hormonal therapy. Among the 3808 women included, 1055 patients had HER2-negative disease, and 2753 patients were HER2-low. Among HER2-low patients, 37 had pathological complete response (CR), and 1097 had pathologic response (PR). Among HER2-negative patients, 11 had pathological CR, and 387 had PR. Multivariable logistic models revealed that age, duration of NET, and HER2 status were significant predictors of any response to NET. HER2-low tumors were more likely to have any response compared to HER2-negative. HER2-low status had improved response to NET among women with early-stage HR+ breast cancer, which supports the concept of HER2-low disease as a distinct therapeutic entity and may inform individualized treatment strategies for endocrine-based therapies.