Assessment of the Androgen Receptor in Older Women with Primary Breast Cancer: Association with a Panel of Biomarkers and Breast Cancer Specific Survival.

Abstract

Breast cancer in older women tends to have more favourable biology, compared to younger women. Androgen receptor (AR) is significant for breast tumour carcinogenesis; however, the role of AR in older women has not been fully explored. Surgical specimens were obtained from an existing series of 1758 older women (≥ 70years) with primary breast cancer, treated in a single institution with long-term (≥ 37years) follow-up. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and a panel of 24 biomarkers was measured by immunohistochemistry (IHC) in these TMAs. AR positivity was assessed by IHC and defined as H-score ≥ 40. The relationship between AR in this cohort was compared to an equivalent group of younger women (< 70years, n = 1708); the panel of 24 biomarkers and breast cancer specific survival (BCSS) in the older cohort. AR was assessed in 509 samples. Overall, 59% of the older women cohort had positive expression of AR, compared to 63% in the younger cohort. AR positivity (regardless of age) was associated with smaller size of tumour, lower grade of tumour, lower tubule formation, lower nuclear polymorphism and lower mitotic frequency. AR positivity was associated with positive expression of oestrogen receptor (ER), progesterone receptor (PR), breast cancer gene1 (BRCA1), cytokeratin (CK) 7/8, CK18, CK19, Bcell lymphoma (Bcl)2 and Mucin1 (Muc1) expression. Conversely, AR-positive expression was associated with negative expression of human epidermal growth factor receptor2 (HER2), Ki-67, CK5, CK17, epidermal growth factor receptor (EGFR), and CD44 expression. Older women with AR-positive tumours had better BCSS compared to AR-negative tumours (p = 0.009). There was no difference in AR expression between older and younger women with breast cancer. AR has prognostic potential in terms of BCSS. Further work is needed to investigate AR as a therapeutic target.