Assistant Professor of Medicine, Harvard Medical School
Clinical Director, Breast Oncology Center
Dana-Farber Cancer Institute
Co-Investigator: Eric P. Winer, MD, Dana-Farber Cancer Institute, Boston, MA
Among women with metastatic breast cancer, 10% to15% will eventually develop brain metastases (cancer that has spread to the brain). In patients with more aggressive tumor subtypes (for example, HER2-positive or triple negative), the risk of brain metastases may reach as high as 25 to 46 percent. Treatment options for patients with breast cancer and brain metastases are limited, and very few drugs have been tested in this setting. Over the past several years, with support from the BCRF, Drs. Nancy Lin, Eric Winer, and colleagues have completed multiple clinical trials to test potential new treatments for patients with advanced breast cancer, including patients with cancer that has metastasized (spread) to the brain. Recently, they reported data from a phase 2 clinical trial testing the role of bevacizumab (Avastin) given in combination with conventional chemotherapy. They found that that over 60% of patients experienced significant tumor shrinkage in the brain metastases and that many of the responses were long-lasting. Based on these promising results, Drs. Lin and Winer are planning a large phase 3 clinical trial to test the value of bevacizumab in this patient population who have few standard treatment options. They have also nearly completed enrollment to a clinical trial of the oral HER2-blocking medicine, neratinib, in patients with breast cancer brain metastases and anticipate the first results may be available within the next year. Finally, in collaboration with other researchers in the context of the EMBRACE (Ending Metastatic Breast Cancer for Everyone) cohort study, Drs. Lin and Winer have developed several new laboratory models for breast cancer brain metastases and are in the process of testing combinations of novel targeted treatments, with the goal of identifying the most promising combinations to push forward into clinical testing.
Drs. Eric Winer, Nancy Lin, and colleagues are taking a multi-pronged and multi-disciplinary approach to evaluate mechanisms of resistance to currently available treatments and to translate those findings to clinical trials, including, but not limited to, patients with cancer that has metastasized (spread) to the brain. The research team has created multiple new laboratory models derived from human tumor tissues collected at the time of surgery, including models specifically designed to test novel drug combinations in the setting of HER2-positive breast cancer and brain metastases. The team is also testing two different targeted combinations in clinical trials for patients with brain metastases. As a new project over the past year, BCRF funding is allowing the research team to continue to build the EMBRACE study, which is a registry study for patients with metastatic breast cancer, designed to capture information about patients’ treatments and response to treatments as well as permission to study their tumor issues, in order to learn from all patients, regardless of whether or not they are participating in a clinical trial of new treatments. The scientific goal of the study is to study important clinical questions with human tissue specimens. Examples of such questions include why and how tumors become resistant to hormonal therapies, why trastuzumab (Herceptin) works extraordinarily well in some patients but not others, etc. To date, the study has enrolled 600 women and men living with metastatic breast cancer, and it is anticipated that the study will provide a rich resource for scientific inquiry in the years to come.
Dr. Nancy Uan-Tsin Lin is a medical oncologist at Dana-Farber Cancer Institute, Clinical Director of the Breast Oncology Center at Dana-Farber, and Assistant Professor of Medicine at Harvard Medical School. Dr. Lin received her medical degree at Harvard Medical School and subsequently completed her residency in Internal Medicine at Brigham & Women’s Hospital and a fellowship in Hematology/Oncology at Dana-Farber/Partners Cancer Care. Dr. Lin’s focus is on developing novel targeted therapies for patients with advanced breast cancer and on exploring opportunities to overcome drug resistance. She is the Principal Investigator of numerous clinical trials for patients with metastatic breast cancer.
Dr. Lin’s honors include a Young Investigator and Career Development Awards from the American Society of Clinical Oncology (ASCO) and the George Canellos Award for Excellence in Clinical Investigation and Clinical Care. She is a member of the Massachusetts Medical Society, American Society of Clinical Oncology, Alliance for Clinical Trials in Oncology, Translational Breast Cancer Research Consortium (TBCRC), and the European School of Oncology Metastatic Task Force.