Targeting HER2/HER3 Co-mutations in Metastatic Breast Cancer: Case Reports of Exceptional Responders to Trastuzumab and Pertuzumab Therapy

Cancer Reports Manuscript
Authors Page E. Blas, Esther San Roman Rodriguez, Heather L. Williams, Maren K. Levin, Joshua S. K. Bell, Mariaelena Pierobon, Alexander S. Barrett, Emanuel F. Petricoin, and Joyce A. O'Shaughnessy


Overexpression of HER2 plays an important role in cancer progression and is the target of multiple therapies in HER2-positive breast cancer. Recent studies have also highlighted the presence of activating mutations in HER2, and HER3 that are predicted to enhance HER2 downstream pathway activation in a HER2-dependent manner.


In this report, we present two exceptional responses in hormone receptor-positive, HER2-nonamplified, HER2/HER3 co-mutated metastatic breast cancer patients who were treated with the anti-HER2-directed monoclonal antibodies, trastuzumab and pertuzumab.


Both patients acheived exceptional responses to treatment, suggesting that combined trastuzumab, pertuzumab, and endocrine therapy could be a highly effective therapy for these patients and our observations could help prioritize trastuzumab deruxtecan as an early therapeutic choice for patients whose cancers have activating mutations in HER2.