November 2019: Androgen receptor expression and response to chemotherapy

Androgen receptor (AR) is discussed as a prognostic and/or predictive marker in breast cancer patients. Previous data has shown that low AR mRNA expression was a predictor for shorter survival in breast cancer patients receiving adjuvant chemotherapy (Witzel et al. J. Cancer Res. Clin. Oncol 2013). This translational research study aimed to investigate the predictive/prognostic values of AR mRNA expression in the neoadjuvant setting. The AR mRNA expression including transcriptional variant 1 (AR1) and 2 (AR2) was analyzed by RT-qPCR in breast cancer patients treated in the neoadjuvant TECHNO (N=118, HER2-positive) and PREPARE trial (N=321, HER2-positive and HER2-negative).

Regarding subtypes, high AR mRNA levels were frequent in HER2-positive (61.3%, 92/150) and luminal tumors (60.0%, 96/160) but almost absent in triple-negative tumors (4.3%, 3/69) (p<0.0001). Overall, high AR mRNA levels were associated with lower pathological complete response (pCR) rates (OR=0.77 per unit [95% CI 0.67–0.88], p=0.0002) and better disease-free survival (DFS) (HR=0.57 [95% CI 0.39–0.85], p=0.0054) and overall survival (OS) (HR=0.43, [95% CI, 0.26-0.71], p=0.0011). In the PREPARE trial, a survival difference for patients with high and low AR1 mRNA levels was only observed in the standard chemotherapy arm but not in the dose-dense treatment arm (OS, HR=0.41 [95% CI 0.22-0.74] vs. HR=1.05 [95% CI 0.52-2.13]; p=0.0459).

These findings provided evidence that AR mRNA can predict response to chemotherapy and demonstrated that AR1 isoform may deliver additional information for the prediction of therapy response to dose-dense chemotherapy treatment.

Witzel I, Loibl S, Wirtz R, Fasching PA, Denkert C, Weber K, Lück HJ, Huober J, Karn T, Mackelenbergh MV, Marmé F, Schem C, Stickeler E, Untch M, Müller V. Androgen receptor expression and response to chemotherapy in breast cancer patients treated in the neoadjuvant TECHNO and PREPARE trial. Br J Cancer. 2019 Nov 15. doi:10.1038/s41416-019-0630-3.

Link in PubMed