Nancy U. Lin, MD

Advancing new strategies to prevent and treat breast cancer metastasis to the brain and central nervous system.

Impact

Nearly half of patients with HER2-positive metastatic breast cancer (MBC), 25 to 45 percent of those with triple-negative MBC, and 15 percent of patients with estrogen receptor (ER)-positive MBC will experience brain metastasis. Dr. Lin is focused on developing effective strategies to prevent and treat metastases to the central nervous system (CNS), either to the brain or to the spinal fluid and lining of the brain (leptomeningeal disease, LMD). Most clinical trials exclude patients with brain metastases or LMD, but trials led by Dr. Lin were among the first to include such patients and to demonstrate that systemic targeted treatments can be effective in the brain. Treatments such as lapatinib, tucatinib and neratinib are now options for patients with brain metastasis due to the results of these clinical studies.

Progress Thus Far

Dr. Lin and her team launched a phase II clinical trial, called DATO-BASE, evaluating the efficacy of a promising antibody drug conjugate datopotamab deruxtecan (Dato-DXd, Datroway®) in patients with brain metastasis or LMD. The study is evaluating the efficacy of Dato-DXd in three different groups: ER-positive/HER2-negative breast cancer with brain metastasis, triple-negative breast cancer with brain metastasis, and HER2-negative breast cancer with LMD. The trial has enrolled patients at Dana-Farber Cancer Institute and is now open at Duke University and Miami Cancer Institute. The HER2-negative breast cancer with LMD group reached accrual goal ahead of schedule.

The team’s multicenter registry study is designed to collect and pool demographic, clinical and pathologic data, and biological specimens from patients with MBC and LMD and has registered 21 patients. The primary goal of this study is to rapidly report on real-world activity of diverse therapeutics outside of clinical trials. The availability of this data will allow researchers to learn more about the biology of LMD and to identify potential new targets for drug development. The first external site is activated, and additional sites are anticipated to begin activating soon. The study aims to accrue 60 patients, and they hope to analyze first clinical data sets before the end of the year.

What’s next

In the next year, Dr. Lin and her team will continue accruing patients with ER-positive/HER2-negative and triple-negative breast cancer brain metastasis to DATO-BASE. They will analyze clinical outcomes and perform translational analyses within the third group that already completed accrual: HER2-negative breast cancer with LMD.

The team will continue accruing patients to the LMD registry, and they will investigate a potential academic and industry collaboration developing a new technology that determines intrinsic breast cancer subtype and receptor status from cerebral spinal fluid.

Finally, the team will focus on a newly launched clinical trial (SAPPHO) evaluating a regimen of multiple HER2-targeted treatments in newly diagnosed patients with HER2-positive metastatic breast cancer. The trial is designed to help investigators understand whether first intensifying therapy for a specific period and then stopping treatment is safe and effective for participants. This trial could lead to curative treatments, including prevention of brain metastasis altogether.

Biography

Nancy Lin, MD is a medical oncologist at Dana-Farber Cancer Institute (DFCI) and 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 the Women in Oncology Award from Practical Recommendations in Immuno and Medical Oncology, and 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.