Androgen Receptor Is Expressed in the Majority of Breast Cancer Brain Metastases and Is Subtype-Dependent

SIMPLE SUMMARY: Androgen receptor (AR) is a receptor found on many breast cancer cells, and drugs can be used to target AR in the treatment of advanced breast cancers. We aim to better understand how AR is expressed in breast cancer that has spread to the brain, i.e., brain metastases (BrM). We used a technique called immunohistochemistry to study AR expression in BrM from 57 breast cancer patients. We found that AR was expressed in the majority of BrM, and was expressed at different frequencies across different types of breast cancer. We did not find an association between AR expression and measures of survival. In most patients, AR expression in breast tumours and BrM was comparable. This study shows that AR is expressed in the majority of breast cancer BrM, and may be a useful target for treating breast cancer patients who have BrM. ABSTRACT: We aimed to evaluate the expression of the “targetable” androgen receptor (AR) in breast cancer brain metastases (BrM). An established, retrospective 57-patient cohort with metastatic breast cancer who underwent surgery for BrM at the Sunnybrook Odette Cancer Centre between 1999–2013 was studied. AR expression in BrM samples was assessed in triplicate using immunohistochemistry (IHC). AR positive status was defined as nuclear AR expression ≥ 10% by IHC using the SP107 antibody. The median age of patients was 52 years (range 32–85 years). 28 (49%) of BrM were HER2+, 17 (30%) were hormone receptor positive (HR+)/HER2−, and 12 (21%) were triple negative breast cancers (TNBCs). 56% (n = 32/57) of BrM were AR positive, and median AR expression was 20% (CI 1.6–38.3%). AR expression was different across breast cancer subtypes; AR was most frequently expressed in HER2+ (n = 21/28), followed by HR+/HER2− (n = 9/17), and lowest in TNBC (n = 2/12) BrM (p = 0.003). Patients with AR positive versus AR negative BrM had similar overall survival (12.5 vs. 7.9 months, p = 0.6), brain-specific progression-free survival (8.0 vs. 5.1 months, p = 0.95), and time from breast cancer diagnosis to BrM diagnosis (51 vs. 29 months, p = 0.16). AR is expressed in the majority of breast cancer BrM and represents a potential therapeutic target.