Striking Back at Trastuzumab Resistance in Breast Cancer

A new strategy is directed at a convergence point for several HER2 signaling pathways.

Successfully targeting human epidermal growth factor receptor 2 (HER2) with the monoclonal antibody trastuzumab represents one of the most important therapeutic advances for patients with HER2-positive breast cancer. Nonetheless, only about 26% of patients with metastatic HER2-positive tumors respond to single-agent trastuzumab, and 40% to 60% respond to trastuzumab plus chemotherapy. Furthermore, almost all patients who initially respond develop resistance to trastuzumab-containing regimens. Many mechanisms of de novo and acquired resistance have been proposed, and more than one mechanism can act in the same patient or even in the same tumor.

Mechanisms of de novo resistance include mutations in the phosphoinositide 3 kinase (PI3K) pathway,…

Reviewing Author

William J. Gradishar, MD

Disclosures

Consultant/Advisory BoardLilly; AstraZeneca; Gilead

Grant/Research SupportBreast Cancer Research Foundation

Editorial BoardsClinical Breast Cancer; Oncology; Annals of Surgery; Breast Cancer Research and Treatment

Leadership Positions in Professional SocietiesNational Comprehensive Cancer Network (Chair, Breast Cancer Panel); American Board of Internal Medicine (Medical Oncology Board)