Pooled clinical trial analyses evaluating outcomes of HER2-low vs HER2-0 expression in patients with metastatic breast cancer following chemotherapy.

The therapeutic importance of subsetting patients with HER2-negative breast cancer according to their tumors' cellular HER2 expression (e.g., HER2-low vs. HER2-0) is relatively new, stemming from the dramatic results of the DESTINY-04 trial which established HER2-low expression as actionable. Most prior observational research of traditionally HER2-negative patients suggests that tumor behavior and biology do not vary according to HER2-low vs. HER2-0 expression, though some studies suggest otherwise. Here we studied this question in women with metastatic breast cancer (MBC) who were treated with standard single agent chemotherapy in the setting of clinical trials carried out in the pre-DESTINY-04 era. After pooling data from 142 female patients with MBC across historic clinical trials and categorizing them according to HER2 expression (i.e., HER2-0 or HER2-low), we evaluated associations between HER2 expression and the outcomes of both progression-free survival (PFS) and overall survival (OS) with both Kaplan-Meier and Cox proportional hazards methods. Studying data from an era when quantifying amounts of tumor HER2 expression in HER2-negative patients was neither standardized nor clinically actionable, we found no meaningful clinical differences in PFS or OS according to HER2-low vs. HER2-0 status, supporting prior findings of no biologic differences.