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. 2016 Jan 12;114(1):14-20.
doi: 10.1038/bjc.2015.434.

Clinical verification of sensitivity to preoperative chemotherapy in cases of androgen receptor-expressing positive breast cancer

Yuka Asano  1 , Shinichiro Kashiwagi  1 , Naoyoshi Onoda  1 , Kento Kurata  1 , Tamami Morisaki  1 , Satoru Noda  1 , Tsutomu Takashima  1 , Masahiko Ohsawa  2 , Seiichi Kitagawa  3 , Kosei Hirakawa  1
Affiliations

Clinical verification of sensitivity to preoperative chemotherapy in cases of androgen receptor-expressing positive breast cancer

Yuka Asano et al. Br J Cancer. .

Abstract

Background: Triple-negative breast cancer (TNBC) patients testing positive for androgen receptor (AR) expression are thought to be chemotherapy resistant, similar to other hormone receptor-positive breast cancers; however, this has not been substantially validated in the clinic. In this study, we investigated the association between chemotherapy sensitivity and AR expression in patients treated with neoadjuvant chemotherapy (NAC) using standardised chemotherapy criteria and regimens.

Methods: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Oestrogen receptor, progesterone receptor, HER2, Ki67 and AR status were assessed immunohistochemically.

Results: Sixty-one patients were diagnosed with TNBC; AR expression was identified in 23 (37.7%), which was significantly less common than that found in non-TNBC patients (103 of 116; 88.8%; P<0.001). The rate of pathological complete response after NAC was significantly lower (P=0.001), and disease recurrence was more common (P=0.008) in patients with AR-positive compared with those with AR-negative TNBC. In TNBC cases, as expected, the non-recurrence period in cases that were negative for AR expression was significantly extended (P=0.006, log-rank).

Conclusions: Androgen receptor expressions may be useful as biomarkers to predict treatment responses to NAC in TNBC. Moreover, induction of a change in subtype to the AR-negative phenotype was observed after NAC.

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Figures

Figure 1
Figure 1
Immunohistochemical analysis of androgen receptor (AR) expression. AR expression was semiquantitatively analysed according to the percentage of cells showing positive expression in the nucleus: 0, 0% (A); 1+, 1–29% (B); 2+, 30–69% (C); 3+, ⩾70% (D). Androgen receptor expression was considered positive when scores were ⩾1, and negative when scores were 0.
Figure 2
Figure 2
Analysis of all 177 patients treated with neoadjuvant chemotherapy (NAC) revealed no significant difference in disease-free survival (DFS) associated with AR expression (P=0.090, log-rank) (A). No significant difference in DFS according to AR expression was observed in patients with non-TNBC (P=0.628, log-rank) (B). A significantly shortened non-recurrence period was observed in patients with AR-expressing tumours, when the analysis was limited to patients with TNBC (P=0.006, log-rank) (C).
Figure 3
Figure 3
Analysis of overall survival (OS) revealed similar observations according to the subtypes and AR expression status of the breast cancer (A–C).
See this image and copyright information in PMC

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