BIOM-07. EXPRESSION OF ANDROGEN RECEPTOR AND PROGRAMMED DEATH-LIGAND 1 IN BREAST-TO-BRAIN-METASTASES.

Abstract

Abstract INTRODUCTION Therapies targeting androgen receptors (AR) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated intracranial activity. In this study, we analyzed the expression of AR and PD-L1 in breast cancer brain metastases (BrM) to identify patients who may benefit from anti-androgenic or anti-PD-1/PD-L1 therapies. METHODS Consecutive BrM resected in our institution (July 1999-June 2013) that were signed out as breast origin were identified and included from the Anatomic Pathology departmental database. A tissue microarray of BrMs was studied by immunohistochemistry for AR, PD-L1, ER, PR and HER2 (SP107, SP142, SP1, IE2, 4B5; Ventana Medical Systems). HER2 gene amplification was determined by INFORM HER2 DNA and Chromosome 17 (Ventana Medical Systems). Immunohistochemistry was used as a surrogate to determine intrinsic subtypes. RESULTS Among 61 breast cancer BrM with available tissue blocks, AR was expressed in 38 (62%) cases and PD-L1 was expressed in 9 (15%) cases. Among BrMs of luminal A subtype (ER+PR+/-HER2-Ki67< 16%; n=2), 50% expressed AR and none expressed PD-L1. Within the luminal B subtype (ER+/PR+/-), all 15 HER2+ BrM expressed AR (100%), while only 1 expressed PD-L1 (7%). Among HER2- luminal B subtype BrMs (n=16), 50% and 12.5% of cases expressed AR and PD-L1, respectively. In BrM of HER2+ subtype (ER-/PR-; n=14), 71% expressed AR and 14% expressed PD-L1. The frequency of AR+ (30%) and PD-L1+ (30%) cases was equivalent in triple negative BrM (ER-/PR-/HER2-; n=14). CONCLUSION Almost two-thirds of breast cancer BrM expressed AR, while only 15% expressed PD-L1. HER2+ luminal B and HER2+ subtypes were most likely to be AR+. Meanwhile, PD-L1 expression was predominant in the triple negative subgroup. Our data suggests that certain subtypes of breast cancer BrM are more likely to be AR+ or PD-L1+; intracranial efficacy of AR-antagonists and immunotherapy warrants investigation for breast cancer BrM, particularly in biomarker-positive subtypes.