Benefit from adjuvant trastuzumab may not be confined to patients with IHC 3+ and/or FISH-positive tumors: Central testing results from NSABP B-31

Abstract

511 Background: Trastuzumab is a humanized monoclonal antibody targeted to HER2 protein and currently indicated for HER2-positive breast cancer defined by overexpression of HER2 protein (3+ IHC staining by HercepTest™) or HER2 gene amplification (HER2/CEP17 ratio over 2 by PathVysion® FISH assay). These criteria were determined for advanced disease but have not been formally tested in the adjuvant setting. We examined these tests’ ability to predict benefit from adjuvant trastuzumab in NSABP trial B-31. Methods: All available tumor tissue blocks from the B-31 trial were subjected to HercepTest and PathVysion assay as defined in the B-31 protocol. Formal statistical test of interaction between HER2 levels measured by these two tests and benefit from trastuzumab was performed. Results: 207 of 1,795 cases (11.5%) showed gene amplification as determined by PathVysion, and 255 of 1,662 (15.3 %) showed overexpression as determined by HercepTest. 161 of 1,662 (9.7%) had neither gene amplification nor overexpression. There was a consistent benefit from trastuzumab in every subset defined by IHC or FISH. No statistical interaction was found between DFS benefit from trastuzumab and levels of protein (p=0.26) or HER2 gene copy number (p=0.60). Benefit was observed in patients with tumors that were negative for FISH and had less than 3+ staining intensity on IHC by HercepTest (RR=0.36 [CI: 0.14–0.92] p=0.032). Conclusion: Current definition of HER2 overexpression/gene amplification based on data from advanced disease may need to be modified for the adjuvant setting. [Table: see text] No significant financial relationships to disclose.