The Impact of Androgen Receptor Expression on Neoadjuvant Therapy in HER2-Positive Breast Cancer

Androgen receptor (AR) is widely expressed in breast cancer, but its predictive value in HER2-positive disease remains uncertain. This study evaluated the association of AR expression with neoadjuvant therapy (NAT) response and survival in HER2-positive breast cancer.

We retrospectively reviewed 336 patients with primary HER2-positive breast cancer treated with NAT at the First Affiliated Hospital of Chongqing Medical University between December 2020 and July 2024. After screening, 210 patients were included. Clinicopathological characteristics, treatment response, and survival outcomes were analyzed. Factors associated with pathological complete response (pCR) and disease-free survival (DFS) were assessed using logistic regression and Cox proportional hazards models. The predictive value of AR expression, as well as AR/ER and AR/PR ratios, was also explored.

The overall pCR rate was 51.9% (109/210). In the overall cohort, higher AR expression was associated with pCR, but not with DFS or overall survival (OS). Multivariate analysis identified T stage, HER2 status, and AR expression as independent predictors of pCR. In exploratory subgroup analyses, the association between higher AR expression and improved treatment response was mainly observed in hormone receptor-negative/HER2-positive patients, in whom higher AR expression was associated with both a higher pCR rate and better DFS. No significant differences in treatment response or survival according to AR expression were observed in the HR+/HER2+ subgroup. Higher AR/ER and AR/PR ratios were associated with better treatment response, whereas the direct associations between AR expression and ER/PR levels appeared limited.

Higher AR expression was associated with improved neoadjuvant treatment response in HER2-positive breast cancer, particularly in the hormone receptor-negative subgroup. However, given the retrospective single-center design and inconsistent findings in the overall population, the clinical value of AR assessment remains preliminary and requires validation in larger prospective studies.