P95HER2 as a predictive marker in the phase III randomized HERNATA trial of trastuzumab and chemotherapy as first-line therapy to metastatic or locally advanced HER2-positive breast cancer.

559 Background: HER2+ tumours express a series of carboxy-terminal HER2 fragments (CTFs or p95HER2) lacking the receptor extracellular domain that have been investigated as a potential trastuzumab resistance marker. Utilizing patients with locally-advanced or metastatic HER2+ breast cancer enrolled in the randomized HERNATA study, we assessed the expression of p95HER2 and its association with time to progression (TTP). Methods: Immunohistochemical (IHC) staining for p95HER2 was performed using a monoclonal antibody that specifically recognizes 611-CTF variant, blinded to clinical outcome (bioTheranostics Inc.). All slides were scored in consensus with a pre-defined cut-point (10% cells of strong staining) to define positive P95HER status. Additionally, an H-score (0-300) based on IHC staining was calculated with a preselected cut-point, that ensured 30% of the patient to be classified p95HER2 positive. TTP was analysed by Cox proportional hazards models. The model assumption of proportional hazards was in...