Nancy U. Lin, MD

Treatment options for patients with breast cancer and brain metastases (cancer that has spread to the brain) are limited, and very few drugs have been tested in this setting. Over the past several years, with support from BCRF, Drs. Nancy Lin, Eric Winer, and colleagues have completed four clinical trials focused upon new treatments for patients with breast cancer brain metastases and are currently testing two new targeted treatment strategies in clinical trials. Collectively, these studies represent a major effort to improve the outcomes in patients with this very challenging complication of breast cancer.

Over the coming year, Drs. Lin and Winer will continue and expand their efforts. It is anticipated that the ongoing trial evaluating carboplatin and bevacizumab will complete accrual within the next 12 months. A trial of neratinib recently opened within the Translational Breast Cancer Research Consortium (TBCRC), a group uniting the clinical trial efforts of 17 leading breast cancer programs in the US.

In addition, Drs. Lin and Winer will embark on several new projects. Dr. Lin is currently co-chairing the RAND (Response Assessment in Neuro-Onology) brain metastasis working group, which aim to improve the quality of clinical trials conducted in this area. Finally, Drs. Lin and Winer have initiated a new collaboration to conduct a series of preclinical studies in laboratory models of HER2-positive brain metastases to identify promising new approaches to translate into the clinic.

Mid-year Progress: Among women with metastatic breast cancer, 10-15% will eventually develop brain metastases. In patients with more aggressive tumor subtypes (for example, HER2-positive or triple negative), the risk of brain metastases may reach as high as 25-46 percent. Although standard options, such as radiation treatment to the brain, are effective, they are associated with both short- and long-term side effects. There is a paucity of data regarding long term neuro-cognitive outcomes after whole brain radiation, and the question of when to use whole brain radiation in patients with three or fewer brain metastases is thus a major question in the field. Additionally, a subset of women will subsequently develop worsening brain metastases despite standard measures. For such women, treatment options are limited. Notably, there are no FDA-approved systemic therapies in this setting. Furthermore, clinicians' ability to predict which patients are at risk for the development of brain metastases is limited, and there are no proven strategies to prevent this devastating complication of cancer.

In the first half of 2011-2012 research period, this research team has made progress on several fronts. They are continuing to define risk factors for central nervous system (CNS) relapse. They are observing patients with HER2-positive, metastatic breast cancer, treated at Dana-Farber and found that in a modern patient population, that over half of patients develop CNS metastases at some point in the course of their disease. This contrasts to about one-third in somewhat older data from the late 1990's/early 2000 era and speaks to the clinical need to identify better approaches for treatment of this patient population. This team plans to submit a manuscript describing this work within the next few months. In addition, these investigators are conducting ongoing analyses in the National Comprehensive Cancer Network (NCCN) breast cancer outcomes database. They have recently found that among patients with HER2+ breast cancer, that hormone receptor-negative/HER2+ patients experience a higher rate of CNS as first site of relapse.

A major area of controversy in the breast cancer field is whether or not to employ routine whole brain radiotherapy (WBRT) in patients who present with a limited number of CNS lesions. The controversy is fueled, in part, by the striking lack of prospective data with respect to long-term neuro-cognitive outcomes. Drs. Lin and Winer's team has opened a study that includes central assessment of radiographic response and standardized collection of neurocognitive outcomes, neurological symptoms, and quality of life. The University of North Carolina-Chapel Hill and Northwestern University will also participate in this study.

In addition, this team continues to conduct clinical trials on novel therapies, among which include sagopilone, lapatinib, carboplatin, bevacizumab, and GRN 1005. These investigators also continue to design new clinical trials for patients with brain metastasis.

Finally, in a new collaboration with Dr. Jean Zhao, the research team has developed several laboratory models of breast cancer brain metastases and will use these models to test novel drugs and combination approaches in order to identify the most promising regimens to evaluate in the clinic.

All of these studies combined will help improve care for breast cancer patients who experience brain metastasis.

Bio:
Dr. Lin is a medical oncologist at Dana-Farber Cancer Institute (DFCI) 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. In 2005, she joined the staff of the Breast Oncology Center at DFCI.

Dr. Lin's focus is on developing novel targeted therapies for patients with advanced breast cancer and exploring mechanisms of drug resistance, with a particular interest in patients with breast cancer that has metastasized to the brain. Dr. Lin is leading multiple ongoing and planned clinical trials evaluating a variety of targeted approaches in patients with metastatic breast cancer. Her work is highly collaborative and involves close working relationships with clinicians, laboratory investigators, and patient advocates. Dr. Lin's honors and awards include a Young Investigator Award and Career Development Award from the American Society of Clinical Oncology. She is a member of the Massachusetts Medical Society, American Society of Clinical Oncology, Alliance for Clinical Trials in Oncology, and Translational Breast Cancer Research Consortium. She is co-chair of the Breast International Group-North American Breast Cancer Group metastatic working group and the Response Assessment in Neuro-Oncology Brain Metastasis working group.