Association of ERBB2 mRNA expression in advanced HER2-positive breast cancer with efficacy of T-DM1

In advanced HER2-positive breast cancer, the 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. HER2DX is a novel test to determine the expression of the ERBB2 gene at the mRNA level. A study in Spain and Italy found that among HER2+ aBC patients receiving T-DM1 the ORR was 0%, 29%, and 56% in the groups with low, medium, and high HER2DX mRNA expression ERBB2 mRNA, respectively (p<0.001). ERBB2 mRNA was significantly associated with better PFS (p=0.002 and OS (p=0.02). The authors conclude that HER2DX provides prognostic and predictive information following T-DM1 for HER2+ aBC.