Biomarker changes associated with the development of resistance to aromatase inhibitors (AIs) in ER-positive breast cancer.

1034 Background: Development of resistance to third-generation AIs is an important problem in ER+ve breast cancer. Several mechanisms have been identified in vitro (e.g., loss of ER expression, activation of signaling pathways independent of ER and acquisition of ER hypersensitivity), but there are no clinical data to support these. The aim of this study was to determine changes in key biomarkers expression (ER, PgR, HER2, and Ki67) in patients who had developed resistance to an AI treatment for ER+ve breast cancer. Methods: Patients with ER+ve breast cancer who had relapsed or progressed while on an AI for whom pathological material was available pre- and post- treatment were identified from the Royal Marsden Hospital database. IHC for ER, PgR, HER2, and Ki67 was performed. ER and PgR were scored by histoscore, Ki67 as % of cells positive and HER2 was scored following CAP/ASCO guidelines (HER2-positive if IHC=3+ ± FISH ratio ≥ 2.20). Results: 43 paired samples were identified. 56% patients received AI in...