Prognostic significance of androgen receptor expression in breast cancer patients undergoing neoadjuvant chemotherapy

Abstract

The androgen receptor (AR) is an emerging biomarker in breast cancer (BC), yet its prognostic relevance in patients undergoing neoadjuvant chemotherapy (NACT) remains inconclusive. While most studies focus on Western populations, data from the Caucasus are scarce. Given regional differences in tumor biology and treatment access, evaluating AR’s clinical significance in these populations is crucial. This study aimed to investigate the association between AR expression, pathological response, and disease-free survival (DFS) in stage II to III BC patients receiving NACT. A retrospective cohort study was conducted on 132 female BC patients treated with NACT at Bonadea Hospital. AR expression patterns were categorized as negative, weak, moderate, or strong. Statistical analyses included chi-square tests, Kaplan–Meier survival analysis, and univariate Cox regression to evaluate associations between AR expression and clinicopathological features, pathological complete response (pCR), and DFS. The median age at diagnosis was 47 years. Invasive ductal carcinoma accounted for 91.1% of cases, with 50.0% of tumors graded as II or III. pCR was achieved in 28.6% of patients. Moderate-to-strong AR expression was observed in 15% of cases and was associated with a significantly lower Ki-67 index (P = .047). Although dichotomized AR expression did not significantly predict DFS (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.08–1.47, P = .151), Cox regression using all 4 AR categories revealed a significant reduction in recurrence risk (HR = 0.384, 95% CI: 0.160–0.918, P = .031). In multivariable model adjusting for estrogen receptor, human epidermal growth factor receptor 2, and Ki-67 expression, moderate-to-strong AR expression remained the most influential prognostic factor, although the association did not reach statistical significance (adjusted HR: 0.31, 95% CI: 0.07–1.41, P = .129; concordance index = 0.83). Among patients with residual disease (non-pCR), moderate-to-strong AR expression was associated with a higher 2-year DFS rate (90.9% vs 46.4%, P = .089). Sensitivity analysis demonstrated no evidence of selection bias related to AR data availability, as 2-year DFS was comparable between patients with and without available AR assessment (76.1% vs 71.6%, log-rank P = .975). Moderate-to-strong AR expression may be associated with improved DFS in patients treated with NACT, especially in those with incomplete pathological response. These findings highlight the potential of AR as a prognostic biomarker and therapeutic target, warranting validation in prospective studies.