Adrienne G. Waks, MD
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 antibody 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. For her Conquer Cancer study, supported by BCRF, Dr. Waks and her team are exploring how HER2 antibody therapies actually work in patients, because they could block tumor progression in two ways: 1) the antibodies can attach to HER2 and block its ability to promote cancer growth, or 2) they can attach to HER2 and signal to the immune system that it should kill HER2-positive cancer cells. The latter process is called antibody-dependent cell mediated cytotoxicity (ADCC), and the team is exploring if this occurs in HER2 antibody-treated patients, and if it correlates with better outcomes.
The team is assessing the immune process of ADCC in tumor biopsy and blood specimens from patients participating in the DAPHNe trial, in which patients were treated with pertuzumab and trastuzumab; different HER2-targeting antibodies. The team found variable immune profiles prior to treatment, which could affect how those tumors respond to antibody therapies. They also identified several immune cell types that differ in the blood between those who responded to antibody therapy and those who did not. Moreover, they found changes in immune cells over the course of treatment, including changes that potentially indicate ADCC activity. This will all build toward generating conclusions on how these therapies work, and how to best design strategies to improve their effectiveness.
They will conduct a similar study in patients enrolled in the MARGOT (NCT04425018) trial comparing the effectiveness of margetuximab, another antibody-based HER2-targeted drug, with trastuzumab. MARGOT is still enrolling patients and will be an important resource in understanding how antibody-based therapies work.
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.
When you give to BCRF, you're funding critical hours in the lab. More time for research means longer, healthier lives for the ones we love.