Background: Triple-negative (TN) breast cancer (BC) patients testing positive for androgen receptor (AR) expression are thought to be chemotherapy resistant, similar to other hormone receptor-positive (HR) BCs. On the other hand, prostate cancer is a hormone-dependent malignant tumor like breast cancer, it has been reported that chemotherapy is more likely to be effective if there is an abnormality in androgen-receptor splice variant-7 (AR-V7). In an immunohistochemical study, as well, AR-V7 expression was reportedly a poor prognostic factor in castration-resistant prostate cancer (CRPC). In this study, we investigated the association between chemotherapy sensitivity and AR-V7 expression in patients treated with neoadjuvant chemotherapy (NAC) using standardized chemotherapy criteria and regimens.

Materials and Methods: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. ER, PgR, HER2, Ki67 and AR-V7 status were assessed immunohistochemically.

Results: In the 43 AR-V7 expression positive group, compared to the 133 negative group, TNBC (p <0.001) and non-HRBC (p = 0.001) were significantly more frequent, and the pCR rate were significantly higher (p<0.001). Among the 61 TNBC and the 80 HRBC patients, the pathological complete response (pCR) rate was significantly higher in AR-V7 expression positive group than in the negative group (p = 0.008) (p = 0.018). Analysis of all 177 patients receiving NAC revealed that no significant difference in disease-free survival (DFS) was associated with AR-V7 expression (p = 0.080, log-rank). However, a significantly extended non-recurrence period was observed in patients with AR-V7-expressing tumors compared to AR-V7 negative tumors, when the analysis was limited to patients with TNBC (p = 0.016, log-rank). In univariate analysis, AR-V7 expression made a significant contribution to extending disease-free survival in patients with TNBC (p = 0.044, hazard ratio = 0.121). However, multivariate analysis indicated that AR-V7 expression was not an independent factor (p = 0.083, hazard ratio = 0.158).

Conclusion: These findings show that AR-V7 expression is a therapeutic effect predictive marker in BCNAC, and indicates particularly high chemotherapy sensitivity in TNBC.

Citation Format: Yuka Asano, Shinichiro Kashiwagi, Wataru Goto, Kento Kurata, Tamami Morisaki, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Sayaka Tanaka, Masahiko Ohsawa, Masaichi Ohira, Kosei Hirakawa. Clinical significance of expression of androgen-receptor splice variant-7 (AR-V7) in neoadjuvant chemotherapy for breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3939.