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Adrienne G. Waks, MD

Medical Oncologist
Dana‐Farber Cancer Institute
Boston, Massachusetts
Conquer Cancer, the ASCO Foundation 

Current Research

Goal: To determine the clinical and immunologic activity of a novel anti- HER2 antibody therapy in early‐stage HER2‐positive breast cancer.

Impact: Anti‐HER2 antibody medicines like trastuzumab (Herceptin®) use a variety of mechanisms, including activation of the body’s own immune system against HER2‐positive breast cancer cells. This results in a cascade of immune system events culminating with the destruction of HER2-positive breast cancer cells. However, there has been limited investigation into the level of immune system activation that occurs following treatment with anti‐HER2 treatment and how this impacts patients’ outcomes. Dr. Waks is conducting studies to assess 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.

What’s next: Dr. Waks and her team will assess the immune process of ADCC in tumor biopsy and blood specimens from patients treated with either the margetuximab or trastuzumab regimens, and explore how the activation of a patient’s immune system against their breast cancer—as measured by ADCC—may correlate with their cancer outcomes.

HER2-positive breast cancer is driven by abnormal signaling from the gene HER2 and accounts for 20 percent of the breast cancer cases diagnosed each year in the United States. Although HER2‐targeted medicines are effective in many cases and have transformed outcomes for HER2-positive breast cancer patients, further optimizing anti‐HER2 treatment strategies is needed to boost their efficacy and save more patients’ lives. Dr. Waks is characterizing a novel anti-HER2 antibody and determining if its activation of the immune system correlates with better patient outcomes.

Full Research Summary

Research Area: Investigating the clinical and immunologic activity of a novel anti- HER2 antibody therapy in early‐stage HER2‐positive breast cancer and determining if immune activation correlates with cancer outcome. 

Impact: 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 have transformed outcomes for HER2-positive breast cancer patients but optimizing anti‐HER2 treatment strategies is needed to boost their efficacy and save more patients’ lives. Anti‐HER2 antibody medicines like trastuzumab (Herceptin) use a variety of mechanisms, including activation of the body’s own immune system against HER2‐positive breast cancer cells. This process, “antibody‐dependent cell mediated cytotoxicity” (ADCC), is initiated by drugs such as trastuzumab and results in a cascade of immune system events that culminates in the destruction of HER2-positive breast cancer cells. However, there has been only limited investigation of how much ADCC is activated following treatment with anti‐HER2 antibody medicines, and how this impacts patients’ outcomes. Dr. Waks is conducting studies to assess 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.

Current research: As part of her Conquer Cancer, the ASCO Foundation study, supported by BCRF, Dr. Waks and her team will conduct a clinical trial to compare trastuzumab and margetuximab (each in combination with paclitaxel and pertuzumab) in HER2-positive cancer patients.  The novel anti‐HER2 antibody margetuximab, a slightly modified derivative of trastuzumab, was designed to allow more effective killing of HER2-positive breast cancer cells through ADCC. A recent phase III clinical trial in metastatic HER2‐positive breast cancer showed that margetuximab (plus chemotherapy) compared to trastuzumab (plus chemotherapy) led to a modest but significant improvement in the rate of progression of patients’ cancers. Dr. Waks and her team will assess the immune process of ADCC in tumor biopsy and blood specimens from patients treated with either the margetuximab or trastuzumab regimens, and explore how the activation of a patient’s immune system against their breast cancer—as measured by ADCC—may correlate with their cancer outcomes.

Biography

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. She 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. 

BCRF Investigator Since

2020

Area(s) of Focus