Background: The androgen receptor (AR) is widely expressed in breast cancers (BC). Its expression in various BC subtypes is variable. It is found in about 70-90% of ERpositive, 50-60%of HER2-enriched, 20-40%of triple negative BC. The AR/ER ratio may impact prognosis and the response to antiestrogen endocrine therapy (ET), although the prognostic and predictive role of AR in advanced BC is still unclear. Methods: We determined whether AR in primary tumors and/or matched metastases is a predictor of efficacy of first-line antiestrogen ET in advanced BC. 102 Patients treated with first-line ET (2002-2011, 93% were treated with an aromatase inhibitor), excluding those receiving concomitant chemotherapy or trastuzumab or pretreated with >2 lines of chemotherapy were evaluated. ER, progesterone receptor (PgR), Ki67 and AR expression was assessed by immunohistochemistry. A cut-off of-1% immunostained cells was used to determine AR positivity. HER2 status was analyzed by using fluorescent in situ hybridization. AR expression was analyzed in relation to the other conventional biomarkers (ER, PgR, HER2 and Ki67), best response (CR, PR, SD, PD), and time to progression (TTP) (months). TTP was estimated using the Kaplan-Meier method and compared with the log-rank test. Hazard ratios and their 95% confidence intervals (95% CI) were estimated using the Cox regression model. The Chi-square test was used to evaluate correlations between categorical variables and best response. p values< 0.05 were considered statistically significant. Results: Biomarkers were determined in primary tumors in 70 cases, in metastases in 49 and in 17 in both. Median TTP was 17 months (95% CI 14-21.5, median follow-up 75 months). The overall concordance rate for AR expression between primary tumors and metastases was 64.7% (95% CI 42%-87.4%). Differences in TTP according to AR status were not statistically significant. 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 PD as best response. Using a cut off of-10% for AR expression, results did not change. In contrast, Ki67 -20% showed a significant association with PD as best response. PgR <1% showed a non-significant association with PD as best response (p=0.079), while significant results (p=0.031) were obtained by using PgR -10% as cut off value. Conclusions: AR expression did not seem to be useful in predicting the efficacy of ET in advanced BC. Conversely, Ki67 and PgR were more accurate predictive biomarker than AR.
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Ravaioli, S., Rocca, A., Bronte, G., Puccetti, M., Tumedei, M. M., Scarpi, E., … Bravaccini, S. (2017). Is Androgen Receptor a predicitive biomarker of response to antiestrogen therapy in advanced breast cancer? Annals of Oncology, 28, vii22. https://doi.org/10.1093/annonc/mdx511.025