Abstract B251: Androgen receptor expression can predict benefit of tamoxifen treatment in patients with ER negative breast cancer.

Abstract

Abstract The androgen receptor (AR) is frequently expressed in normal breast epithelium and in a substantial fraction of malignant breast tumors, even though the importance of AR in breast cancer is not established. In estrogen receptor (ER) positive breast cancer, AR binds to estrogen responsive element and inhibits proliferation, on the contrary in ER negative and HER2 positive cells AR activates the Wnt and HER2 pathways and induces proliferation. There are several therapies against the ER pathway and resistance to treatment is a big problem, targeting AR may be one alternative for some of these patients. In this study, we investigate the role of AR protein expression with immunohistochemistry in a defined cohort of 912 lymph node negative post menopausal breast cancer patients with a long follow up period randomized to no endocrine treatment or tamoxifen independent of ER expression, to examine if AR is a prognostic factor and/or predictor of tamoxifen treatment. In our cohort 82.4% showed AR expression in the tumour cells. In the case of ER positive patients without tamoxifen treatment, no significant difference was found when grouped by AR status (p>0.05). Tamoxifen treated patients with ER positive tumours showed benefit from the treatment regardless of AR expression (negative cases (p=0.038); positive cases (p=0.00001)). Further, if ER negative tumours from patients treated with tamoxifen were investigated AR expression was a tamoxifen predictive factor (p=0.014) (HR = 0.40 95% C.I. 0.18-0.89; p=0.024) but among cases with ER negative and AR negative tumours treatment with tamoxifen tended to have a worse outcome (p=0.06) HR = 2.26 95% C.I. 0.99-5.15; p=0.053. The multivariate interaction tests was significant (HR = 0.18 95% C.I. 0.056-0.56 p=0.003). There was a significant correlation between expression of the androgen receptor and small tumour size (p=0.002), PgR expression (p<0.001) ER expression (p<0.001), Cyclin D1 (p<0.001) and HOXB13 (p<0.001). The expression of AR was inversely correlated to HER2 (p=0.002). Tamoxifen is known to bind strongly to ER, however there are studies showing that tamoxifen also binds to AR. In prostate cancer, cell growth and AR activity were inhibited by tamoxifen and the ER antagonist fulvastrant effectively down regulates AR in several human prostate cancer cells and induce growth inhibition. These results suggest an anti-androgenic aspect of anti-estrogen. Our results indicate that AR is a tamoxifen predictive factor in ER negative breast cancer and suggest that this group of patients could benefit from tamoxifen treatment. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B251. Citation Format: Erik Hilborn, Jelena Gacic, Tommy Fornander, Lambert Skog, Bo Nordenskjöld, Olle Stål, Agneta Jansson. Androgen receptor expression can predict benefit of tamoxifen treatment in patients with ER negative breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B251.