Correlation of Androgen Receptor Expression with HER2 Status and Treatment Response in Breast Cancer

Manjunath S. Hiremani, Suresh Babu M C, Guruprasad C Shenoy, Lokesh K. N, Rudresha A. H, L. K. Rajeev
Author(s)
1Assistant Professor, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Kalaburagi, Karnataka, India. 2Director of Medical Oncology, Krishna Institute of Medical Sciences, Bengaluru, Karnataka, India. 3Consultant, Department of Medical Oncology, Sri Shankara Cancer Hospital and Research Centre, Bengaluru, Karnataka, India. 4Professor, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India. 5Associate Professor, Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India.

Abstract

Background: Human epidermal growth factor receptor 2 (HER2) expression and androgen receptor (AR) status may influence breast cancer biology and response to neoadjuvant chemotherapy (NACT). The clinical significance of AR expression across Her2 negative, HER2-low, and HER2-positive tumors remains incompletely understood. The objective is to evaluate the association of HER2 status with AR expression and residual cancer burden (RCB) following NACT in patients with breast carcinoma. Material and Methods: This prospective observational study included 268 patients with histologically confirmed invasive breast carcinoma. HER2 status was classified as Her2 negative (IHC 0), HER2-low (IHC 1+ or IHC 2+/FISH-negative), and HER2-positive (IHC 3+ or IHC 2+/FISH-positive). AR expression was assessed by immunohistochemistry, and pathological response following NACT was evaluated using the RCB classification. Results: AR positivity was observed in 168 (62.7%) patients. Of 268 tumors, 115 (42.9%) were Her2 negative, 66 (24.6%) HER2-low, and 87 (32.5%) HER2-positive. AR positivity was significantly more frequent in HER2-low (72.7%) and HER2-positive (72.4%) tumors than in Her2 negative tumors (49.6%; p<0.001). RCB distribution differed significantly according to HER2 status (p=0.024); HER2-low tumors had the lowest RCB-0 rate (10.6%) and highest RCB-III rate (48.5%). AR-negative tumors had a higher RCB-0 rate than AR-positive tumors (31.0% vs 16.7%; p=0.019). Notably, among HER2-low/AR-positive tumors, only 4.2% achieved RCB-0, while 93.8% had RCB-II/III disease. Conclusion: HER2 status was significantly associated with AR expression and pathological response following NACT. The HER2-low/AR-positive phenotype demonstrated particularly high residual disease burden, suggesting that combined assessment of HER2 and AR may identify biologically distinct breast cancer subgroups with differential response to neoadjuvant therapy.

Keywords: Androgen receptor, HER2-low, breast cancer, neoadjuvant chemotherapy, residual cancer burden, HER2, pathological response.

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