HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1

In advanced HER2-positive (HER2+) breast cancer (BC), the new antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is more effective compared to trastuzumab emtansine (T-DM1). However, T-DXd can have significant toxicities, and the right treatment sequence is unknown. Biomarkers to guide the use of anti-HER2 therapies beyond HER2 status are needed. Here, we evaluated if pre-established levels of ERBB2 mRNA expression according to the HER2DX standardized assay are associated with response and survival following T-DM1. In ERBB2 low, medium, and high groups, the overall response rate was 0%, 29% and 56%, respectively (P<.001). ERBB2 mRNA was significantly associated with better progression-free survival (p = 0.002) and overall survival (OS; P = 0.02). These findings were independent of HER2 IHC levels, hormone receptor, age, brain metastasis and line of therapy. The HER2DX risk-score (P=.04) and the immunoglobulin (IGG) signature (P=.04) were significantly associated with OS since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ BC.