HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1
Fara Brasó‐Maristany, Gaia Griguolo, Núria Chic, Tomás Pascual, Laia Paré, Julia Maués, Patricia Galván, Maria Vittoria Dieci, Federica Miglietta, Tommaso Giarratano, Olga Martínez‐Sáez, Mercedes Marín‐Aguilera, Francesco Schettini, Benedetta Conte, Laura Angelats, María Vidal, Bárbara Adamo, Montserrat Muñoz-Mateu, Esther Sanfeliu, Blanca González‐Farré, Ana Vivancos, Patricia Villagrasa, Joel S. Parker, Charles M. Perou, PierFranco Conte, Aleix Prat, Valentina Guarneri
Abstract
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.