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Nancy U. Lin, MD
Associate Professor of Medicine, Harvard Medical School
Associate Chief, Division of Breast Oncology
Dana-Farber Cancer Institute
Goal: To discover strategies to prevent and treat the spread of breast cancer to the brain.
Impact: Therapies for HER2-positive metastatic breast cancer (MBC) can lose their effectiveness, causing the death of many MBC patients. Dr. Lin has conducted successful clinical trials testing two drugs for the treatment of these patients: this has led to FDA-approval for both. Her team will continue to test new treatment approaches which will inform new strategies to improve outcomes for these patients.
What’s next: Her team is now identifying predictors of brain metastases and for central nervous system involvement. In addition, they will examine the efficacy of antibody-drug conjugates in the treatment of patients with active brain metastases.
While therapies targeting HER2 are highly effective in patients with HER2-positive MBC, many patients will die of MBC because treatments lose their effectiveness. This is because they are either ineffective in the brain and/or because the cancer evades the effects of HER2-based treatments in other ways. Dr. Lin is focused on finding more effective treatments for patients with both early-stage and metastatic HER2-positive breast cancer.
Full Research Summary
Research area: Advancing new treatments and prediction strategies for HER2-positive breast cancer patients with brain metastasis.
Impact: Treatments targeting HER2 are highly effective in patients with HER2-positive, metastatic breast cancer (MBC). However, patients still die of MBC because these therapies lose their effectiveness, either because they are ineffective in the brain (a common metastatic site for advanced HER2-positive breast cancer) and/or the cancer is able to escape the effects of HER2-based treatments by other means. Dr. Lin has conducted studies that have led to the FDA-approval of both neratinib and tucatinib for the treatment of HER2-positive MBC. Moreover, her team demonstrated the value of both drugs in treating patients with brain metastases in phase I/II clinical trials. She is now examining antibody-drug conjugates (ADCs) as an effective treatment for these patients and will also undertake investigations to identify genomic predictors of breast cancer related brain metastases and central nervous system involvement.
Current investigation: Dr. Lin and her team are assessing the genomic alterations that occur with the development of breast cancer related brain and central nervous system metastases by utilizing the Ending Metastatic Breast Cancer for Everyone (EMBRACE) research study database – this database contains data from over 2,000 MBC patients. They are also launching a prospective study to examine the central nervous system efficacy of ADCs in patients with HER2-positive MBC.
What she’s accomplished so far: She and her colleagues carried out a clinical trial testing the combination of the anti-HER2 drug neratinib and capecitabine for patients with HER2-positive breast cancer that had spread to the brain. This regimen led to significant tumor shrinkage in half of the patients. Her team also conducted a phase Ib clinical trial to test the anti-HER2 drug tucatinib, and trastuzumab in these patients. This study established the potential intracranial efficacy of tucatinib. These clinical trials led to FDA-approval for both neratinib and tucatinib for treating HER2-positive breast cancer that had spread to the brain. In other studies, Dr. Lin and her team have utilized the EMBRACE database to characterize the genetic alterations associated with breast cancer brain metastases.
What’s next: Dr. Lin and her colleagues will continue their characterization of genetic alterations associated with breast cancer brain metastases and expand this analysis to include those genetic alterations associated with breast cancer-related central nervous system metastases. They hope to identify genomic predictors of brain and central nervous system metastases. In addition, her team will launch a prospective, multicenter study to evaluate the efficacy of trastuzumab-deruxtecan in patients with HER2-positive breast cancer and central nervous system metastases.
Dr. Nancy Lin is a medical oncologist at Dana-Farber Cancer Institute (DFCI) and Associate 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. Since 2018, she has served as Associate Chief of the Division of Breast Oncology 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.