Dr. Hamilton on Overcoming Resistance to HER2-Targeted Therapy in Breast Cancer

Erika P. Hamilton, MD, director, Breast and Gynecologic Research Program, Sarah Cannon Research Institute, discusses overcoming resistance to HER2-targeted therapy in breast cancer.

HER2 resistance is heterogenous, explains Hamilton—–it’s not all one type of resistance. For example, there are patients who have HER2-low tumors. These patients stand in contrast to the traditional woman who comes in with a ratio of 18, indicating that the tumor is completely HER2 driven. These women tend to do very well on HER2-directed agents. For the women with low HER2 expression, other pathways such as HER3, or even PI3K may come into play in the future, says Hamilton. In these patients, combination therapies are likely going to become most effective, she adds.

Some of the newer antibody-drug conjugates (ADCs) are also exciting; [fam-] trastuzumab deruxtecan (DS-8201) is among them. This ADC has shown activity and has been the first to do so dramatically in the HER2-low space, says Hamilton.