Titles and Affiliations

Professor, Department of Surgery
University of Pittsburgh School of Medicine
Director, National Cancer Institute Cooperative Group Clinical Trials
University of Pittsburgh Hillman Cancer Center

On behalf of the National Surgical Adjuvant Breast and Bowel Project (NSABP)

Research area

Understanding what drives treatment response and resistance in patients with HER2-positive breast cancer.


Therapies such as trastuzumab (Herceptin®) have revolutionized the treatment of HER2-positive breast cancer. Trastuzumab and other HER2-targeted therapies block the pro-tumorigenic actions of HER2 on cancer cells and stimulate an immune response directed against the cells. Nevertheless, only a subset of patients with HER2-positive breast cancer experience a robust response and there is a pressing need to understand why some do not. Dr. Wolmark’s BCRF research aims to discover biomarkers to predict treatment response and to elucidate mechanisms of resistance to therapies.

Progress Thus Far

The team recently identified a variant form of HER2 in some HER2-positive tumors from patients who did not have a robust response to HER2-targeting therapies. They also found that this variant of HER2 suppresses immune responses in these tumors, which may help the tumors “hide” from the immune system.  

What’s next

The team is currently assessing the utility of biomarker panels that identify the HER2 variant in patient breast cancer samples, along with other proteins that may interfere with the effectiveness of HER2-targeting therapies. They are also performing imaging analyses of the spatial distribution of immune cells within tumors, to see if that might predict patient response to different types of HER2-targeting therapies. In the coming year, they will explore how HER2 variants drive therapeutic resistance, and how tumors might reduce their production of HER2 as another means of therapeutic escape. 


Dr. Norman Wolmark, MD, is Chairman of  NSABP Foundation, a not-for-profit academic research organization with a nearly 60-year history of conducting ground-breaking research studies in breast and colorectal cancer.

He is also Professor and Chairman of Human Oncology at Drexel University School of Medicine. Dr. Wolmark received his medical degree from McGill University of Montreal, and he completed his residency at the University of Pittsburgh. He served a fellowship in Surgical Oncology at Memorial Sloan Kettering Cancer Center, and he later became a cancer expert at the Surgery Branch of the National Cancer Institute.

Dr. Wolmark belongs to numerous prestigious organizations including the American Society of Clinical Oncology, the American Association of Cancer Research, and the American Surgical Association.

Over his near 45-year tenure as a cancer researcher, Dr. Wolmark is extensively published, with more than 400 scientific journal articles and book chapters in print.  He is a widely sought-after speaker and lecturer in his field and serves on the editorial board of the Journal of Women’s Cancer, The Journal of Clinical Oncology, and numerous advisory boards, and as an advisor to oncology programs, societies, and institutes throughout the United States and abroad.

Devoted to the evolution of large randomized clinical trials for the treatment and prevention of breast and bowel cancers, he is also a reviewer for The Journal of Clinical Oncology and the New England Journal of Medicine, and he is an editorial board member of the Journal of Women's Cancer and Clinical Breast Cancer.

BCRF Investigator Since


Areas of Focus