Dr. Rugo on HER2 Differentiation in Metastatic Breast Cancer

Hope Rugo, MD, professor, medicine, the Division of Hematology and Oncology, director, Breast Oncology, director, Clinical Trials Education, the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, discusses the challenges of differentiating between HER2-low and HER2-negative metastatic breast cancer.

The newly defined HER2-low breast cancer subcategory includes disease that shows a low level of HER2 expression by immunohistochemistry (IHC), with a score of either 1+ or 2+, Rugo says. HER2-low disease expresses a small amount of the HER2 protein, but not enough to be considered HER2-positive, which is defined by the ASCO/CAP guidelines as a score of 3+ by IHC, Rugo explains.

Pathologists can easily differentiate between 2+ and 3+ disease based on the amount of stain that appears on the IHC test, Rugonotes. However, differentiating between 1+ and 0 is more difficult, because IHC results can be considered less than 1+ but still have staining, Rugo says. The process of determining HER2 scores in individual patients is complicated and requires further attention, Rugo concludes.

Dr. Rugo on Prognostic Differences in HER2+ and HER2-low Metastatic Breast Cancer

HER2-positive metastatic breast cancer is both prognostic and predictive of patient response to HER2-targeted therapies, Rugo says. Before HER2-targeted therapy, HER2-positive disease had unfavorable outcomes, and after the advent of HER2-targeted therapy, HER2 positivity dramatically predicted responses, Rugo explains.

Conversely, HER2-low status does not appear to be prognostic, aside from conforming with more general cancer-defining characteristics, Rugo emphasizes. For example, patients with triple-negative breast cancer are less likely to have HER2-low disease than those with hormone receptor–positive disease, Rugo concludes.