Dr. Brufsky Discusses Resistance to HER2-Targeted Therapies

Adam M. Brufsky, MD, PhD, professor of Medicine, associate chief of Hematology/Oncology, co-director of the Comprehensive Breast Care Center, associate director of Clinical Investigation, University of Pittsburgh, discusses resistance to HER2-targeted therapy in breast cancer.

Researchers are still unsure if the resistance seen is to HER2 or if it is to the underlying partner to the HER2 agent. Both the receptor tyrosine kinase and mTOR pathways have been explored with modest results.

Lately, the CDK 4/6 pathway has garnered a lot of interest, says Brufsky, with clinical trials exploring trastuzumab (Herceptin) plus various CDK 4/6 inhibitors.

The challenge, Brufsky adds, is that agents have not been able to penetrate the central nervous system. The brain is a sanctuary site in metastatic disease, and about 50% of women with metastatic breast cancer will develop brain metastases at some point.