Chairman and Principal Investigator, National Surgical Adjuvant Breast and Bowel Project (NSABP)
Professor and Chairman of Human Oncology
Drexel University School of Medicine
Seeking to identify biomarkers to predict response to therapy and prevent drug resistance.
Patient data from clinical trials are used to identify predictive biomarkers to select patients with HER2-positive breast cancers for anti-estrogen therapy.
These studies will inform treatment decisions to improve outcomes for patients with HER2-positive breast cancer.
The development of pharmaceuticals designed to specifically target the molecular drivers of breast cancer has transformed the therapeutic landscape and dramatically improved survival. Perhaps the best example is the development of drugs that target the HER2 protein, which is upregulated in about 20 percent of breast cancer cases.
These agents (e.g., trastuzumab, pertuzumab and others) block the activity of HER2 and also stimulate an immune response that helps to kill the cancer cells. Nevertheless, only a subset of patients with HER2-positive tumors respond robustly. There is a pressing need to understand the resistance mechanisms for the development of strategies to ensure the optimal benefit of HER2-targeting therapies.
The NSABP B-52 clinical trial evaluated patients with HER2-positive breast cancers that were also positive for the estrogen receptor. Pre-clinical studies have suggested that estrogens drive one mechanism for resistance to HER2-targeted therapy. Thus, the B-52 trial tested whether estrogen deprivation therapy with an aromatase inhibitor improves the response to dual HER2 therapy with trastuzumab and pertuzumab.
Results showed only a small improvement in therapeutic response in the majority of patients, but some patients receiving estrogen deprivation showed significant benefit. Understanding how to prospectively identify such patients is crucial. Dr. Wolmark and colleagues will analyze tumor biopsies from B-52 to identify biomarkers that will allow prediction of which patients will benefit most from estrogen deprivation when receiving HER2-targeted therapy.
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.