Androgen receptor in advanced breast cancer: is it useful to predict the efficacy of anti-estrogen therapy?

Abstract

BackgroundAndrogen receptor (AR) is widely expressed in breast cancer (BC) but its role in estrogen receptor (ER)-positive tumors is still controversial. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy (ET).MethodsWe assessed whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line ET in advanced BC. Patients who had received first-line ET (2002–2011) were recruited, while those given concomitant chemotherapy or trastuzumab or pretreated with > 2 lines of chemotherapy were excluded. ER, progesterone receptor (PgR), Ki67 and AR expression were assessed by immunohistochemistry, and HER2 mainly by fluorescent in-situ hybridization. Cut-offs of 1 and 10% immunostained cells were used to categorize AR expression.ResultsAmong 102 evaluable patients, biomarkers were assessed in primary tumors in 70 cases and in metastases in 49, with 17 patients having both determinations. The overall concordance rate between primary tumors and metastases was 64.7% (95% CI 42%-87.4%) for AR status. AR status did not affect TTP significantly, whereas PgR and Ki67 status did. AR/PgR ≥0.96 was associated with a significantly shorter TTP (HR = 1.65, 95% CI 1.05-2.61, p = 0.028). AR status in primary tumors or metastases was not associated with progressive disease (PD) as best response. In contrast, Ki67 ≥ 20% and PgR < 10% showed a statistically significant association with PD as best response.ConclusionsAR expression does not appear to be useful to predict the efficacy of ET in advanced BC, whereas Ki67 and PgR exert a greater impact on its efficacy.

Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer

“…Concerning the discrepancy between the AR status of the primary tumor and CTCs, in our study, we found 85% of the primary tumors positive for AR , which is concordant with the literature . In the study of Bronte et al .…”

“…There are several disadvantages of using IHC to determine the AR status on primary tumors, metastatic lesions or CTC samples. First, different antibodies are being used to measure the AR status and different cut‐offs to determine AR‐protein expression (positive AR expression defined as >0%, ≥1% or ≥10% of the tumor cells being positive) . Also, AR‐protein expression may be a suboptimal marker for response to AR‐targeting therapy since gene expression models seem to predict response to enzalutamide more accurately …”

“…First, different antibodies are being used to measure the AR status and different cut-offs to determine AR-protein expression (positive AR expression defined as >0%, ≥1% or ≥10% of the tumor cells being positive). 16 Also, AR-protein expression may be a suboptimal marker for response to AR-targeting therapy since gene expression models seem to predict response to enzalutamide more accurately. 30,31 Concerning the discrepancy between the AR status of the primary tumor and CTCs, in our study, we found 85% of the primary tumors positive for AR, which is concordant with the literature.…”

“…30,31 Concerning the discrepancy between the AR status of the primary tumor and CTCs, in our study, we found 85% of the primary tumors positive for AR, which is concordant with the literature. 16,32 In the study of Bronte et al 16 AR expression was determined on FFPE tissue of the primary tumor and metastatic lesion with IHC. A tissue was positive if it had ≥1% IHC AR staining.…”

“…3,10,[12][13][14][15] Collectively, these data show that AR-targeting drugs are only active in a subset of patients, stressing the need for biomarkers to identify these patients. Additionally, there is a 35% discrepancy rate between AR-expression in primary breast cancer and metastatic tissue 16 rendering it questionable whether assessment of AR expression on primary tumor tissue is appropriate to select mBC patients for AR-targeting drugs.…”