Adrienne G. Waks, MD
Dana‐Farber Cancer Institute
Conquer Cancer, the ASCO Foundation
Determining the clinical and immunologic activity of a novel anti-HER2 antibody therapy in early-stage HER2-positive breast cancer.
Of the over 250,000 cases of breast cancer diagnosed each year in the United States, approximately 20 percent are driven by abnormal signaling from the gene HER2 and are categorized as HER2-positive breast cancer. HER2-targeted therapies are effective in many cases and transformed outcomes for these patients but optimizing anti-HER2 treatment strategies is needed to boost their effectiveness and save more lives. Anti-HER2 antibody treatments like trastuzumab (Herceptin®) use a variety of mechanisms to kill cancer cells—one includes activation of the body's own immune system against HER2-positive breast cancer cells. This process, called antibody-dependent cell mediated cytotoxicity (ADCC), results in a cascade of immune system events that culminates in the destruction of HER2-positive breast cancer cells. For her Conquer Cancer study, supported by BCRF, Dr. Waks and her team are studying the clinical effectiveness of a novel anti-HER2 antibody, margetuximab, and how its activation of a patient's immune system may correlate with their cancer outcome.
The team will assess the immune process of ADCC in tumor biopsy and blood specimens from patients treated with either the margetuximab or trastuzumab therapeutic regimens. They are collecting data and patient samples from two clinical trials, the first, DAPHNe, just completed its data collection from all patients for the team’s analysis. The second trial, MARGOT, has enrolled 21 of a planned 171 patients.
With all of the information collected from the DAPHNe trial, the team will begin analyzing the samples using a variety of methods, including: RNA sequencing (studying the levels of different genes in the tumor), protein staining (to visualize what proteins are present and where they are present in the tumor), and flow cytometry (to understand the type and activity level of immune cells present in each patient’s bloodstream over the course of their breast cancer treatment). This information will be compared to patient outcomes to see how this molecular information may correlate with patients’ response to therapy and survival.
Adrienne Waks, MD, is a staff physician in breast oncology at the Dana‐Farber Susan F. Smith Center for Women’s Cancers, and an Instructor at Harvard Medical School. She received her medical degree at Harvard Medical School and completed residency training in internal medicine at Brigham and Women’s Hospital in Boston, MA, where she was selected to serve for an additional year as a Chief Resident in internal medicine. She completed a clinical and research fellowship in medical oncology at Dana‐Farber/Partners Cancer Care.
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