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

In advanced HER2-positive (HER2+) breast cancer, the new antibody-drug conjugate trastuzumab deruxtecan is more effective compared with trastuzumab emtansine (T-DM1). However, trastuzumab deruxtecan can have considerable 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 preestablished 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 statistically significantly associated with better progression-free survival (P=.002) and overall survival (OS; P=.02). These findings were independent of HER2 immunohistochemistry (IHC) levels, hormone receptor, age, brain metastasis, and line of therapy. The HER2DX risk score (P=.04) and immunoglobulin signature (P=.04) were statistically significantly associated with overall survival since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ breast cancer.