Nancy U. Lin, MD

2012-2013 BCRF Project:
(made possible by generous support from ANN INC.)

Among women with metastatic breast cancer, 10% to 15% 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 BCRF, Dr. Lin's team has made progress on several fronts.

As clinicians' ability to predict which patients are at risk for the development of brain metastases is limited, Dr. Lin's team has worked towards defining risk factors for central nervous system (CNS) relapse. Based on their clinical experiences, they have observed that the rate of CNS metastases among women with metastatic HER2 positive (HER2+) breast cancer is higher than previously reported, thus underscoring the clinical need to identify better approaches for treatment of this patient population.

Dr. Lin's team has also continued their study following the outcomes of HER2+ or estrogen receptor positive (ER+) breast cancer patients who presented with a limited number of CNS lesions. They have activated a study at Dana-Farber Cancer Institute and University of North Carolina, Chapel Hill, which includes central assessment of radiographic response and standardized collection of neurological symptoms and quality of life. This research builds on the debate in breast cancer care of whether or not to employ routine whole brain radiotherapy in these patients. The striking lack of prospective data with respect to long-term neurocognitive outcomes has been an obstacle in moving this area forward.

They are also carrying out clinical trials of novel therapies, such as iniparib and lapatinib. They have also worked with new drugs that had shown promise in crossing the blood-brain barrier, which is the biggest obstacle in treating brain metastasis patients.

In addition, Dr. Lin is co-chair of the Response Assessment in Neuro-Oncology metastatic working group, whose goal is to develop standard criteria for response assessment in clinical trials of patients with brain metastases from solid tumors. It is expected that this effort will lead to more consistency across trials, allow for a better degree of cross-trial comparisons, and provide a guide to investigators leading trials in this area. These efforts aim to enhance design of future clinical trials for breast cancer patients with brain metastasis.

Dr. Lin also co-chairs the Brain Metastasis Working Group within the North American Breast Group. Monthly telephone calls, coordinated by the National Cancer Institute's Cancer Therapy Evaluation Program, are focused on the design of new clinical trials, discussion of compounds within the CTEP portfolio, harmonization of trial eligibility criteria and trial design, and support of international collaborations.

Mid-year Progress: With BCRF funding, Dr. Lin's team has made progress on several fronts. In their efforts to define risk factors for central nervous system (CNS) relapse, they completed two analyses in the National Comprehensive Cancer Network (NCCN) breast cancer outcomes database. They have confirmed that HER2 and triple negative tumor subtype are associated with brain metastasis. They have also shown that among patients with HER2-positive breast cancer, hormone receptor status further identifies a group of women at risk for CNS as site of first relapse.

A major area of controversy in the field is whether or not to employ routine whole brain radiotherapy (WBRT) in patients who presented 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. To provide much needed information, Dr. Lin's team continues to enroll onto a prospective study that includes central assessment of radiographic response, longitudinal assessment of neuro-cognitive function, neurological symptoms, and quality of life among patients treated with WBRT. The study is open at Dana-Farber, University of North Carolina (UNC Chapel Hill), and Northwestern University. BCRF funds are supporting per patient costs at these sites. In addition, Dr. Lin co-chairs two national working groups focused on brain metastasis. Her leadership of the Response Assessment in Neuro-Oncology metastatic working group has resulted in two manuscripts, which will be submitted for review in mid-February 2013. At least two additional manuscripts are planned.

Dr. Lin's group is also involved in several efforts to help identify novel therapeutic strategies for brain metastases, including efforts to elucidate the development of therapy resistance and to explore ways to overcome this phenomenon.

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.