Dose-dense adjuvant chemotherapy in HER2-low breast cancer: an exploratory analysis of the GIM2 trial

Background Dose-dense (DD) adjuvant chemotherapy represents a standard treatment for patients with high-risk node-positive early-stage HER2-negative breast cancer (BC). In this exploratory analysis of the GIM2 trial, we investigated the efficacy of DD chemotherapy among patients with HER2-negative BC according to HER2 immunohistochemistry (IHC) score. Methods Patients with node-positive early BC were randomized to receive either DD or standard schedule anthracycline- and taxane-based chemotherapy. HER2 status was assessed locally. Tumours with HER2 score 0 were classified as HER2-zero, those with a HER2 score 1+ or 2+ without ISH amplification as HER2-low. Tumours classified as HER2-negative with unknown IHC score were considered as a separate subgroup. Results Overall, 1,243 subjects were eligible for this analysis, with 475 (38.2%) tumours classified as HER2-zero, 446 (35.9%) as HER2-low and 322 (25.9%) as HER2-negative with unknown IHC score. At a median follow-up of 14.9 years (IQR 8.4-16.2), no interaction was observed between treatment effect and HER2 status in invasive disease-free survival (iDFS) (p for interaction=0.42) nor in overall survival (OS) (p for interaction=0.34). Efficacy of DD chemotherapy was observed regardless of HER2 status: among patients with HER2-zero tumours, adjusted hazard ratio (aHR) for iDFS was 0.62 (95% confidence interval [CI] 0.45-0.85) and for OS was 0.55 (95% CI 0.36-0.84). Among patients with HER2-low tumors, aHR was 0.82 (95% CI 0.61-1.11) for iDFS and 0.84 (95% CI 0.57-1.23) for OS. Conclusions In patients with HER2-negative high-risk early BC, the benefit of DD chemotherapy was observed irrespective of HER2 status. (NCT00433420)