作者
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,Esther Sanfeliu,B. González,Ana Vivancos,Patricia Villagrasa,Joel S. Parker,Charles M. Perou,Pierfranco Conté,Aleix Prat,Valentina Guarneri
摘要
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.