Nancy U. Lin, MD

Advancing new strategies to prevent and treat breast cancer metastasis to the brain and central nervous system and exploring whether exceptional responders to treatment can safely reduce therapy.

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. Cancer spread to the spinal fluid and lining of the brain, known as leptomeningeal disease (LMD), is less common but carries a particularly poor prognosis. 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. Dr. Lin is also exploring a different question: whether patients who respond exceptionally well to treatment for many years could safely shift to a less intensive regimen with fewer side effects.

Progress Thus Far

Dr. Lin’s team continues enrolling patients in DATO-BASE (NCT06176261), a phase II trial testing an antibody drug conjugate datopotamab deruxtecan (Dato-DXd, Datroway®) in patients with ER-positive or triple-negative breast cancer that has spread to the brain. The trial’s LMD group has completed enrollment and shown promising results so far, with full results expected soon. The team’s multicenter LMD registry, gathering data and samples to better understand the disease and find new treatment targets, also continues to grow.

Separately, using data from the BCRF-supported EMBRACE (Ending Metastatic Breast Cancer for Everyone) study, the team found that circulating tumor DNA (ctDNA), tiny fragments of tumor DNA, strongly predicted which MBC patients would become “exceptional responders,” remaining progression-free for three or more years on first-line HER2-targeted therapy. This suggests ctDNA testing could help identify patients who might safely reduce treatment intensity.

What’s next

The team will continue enrolling patients in DATO-BASE and the LMD registry, with results expected over the next one to two years. Building on the EMBRACE findings, they’ve launched the REST trial, testing whether exceptional responders with undetectable ctDNA can safely shift to a less intensive regimen, potentially reducing side effects and treatment burden without compromising outcomes.

“Years ago, BCRF supported the first ever trial of a targeted systemic treatment for breast cancer brain metastases. BCRF’s continued support of my work on multiple subsequent trials has improved survival and quality of life in patients facing one of the most devastating sites of breast cancer spread.”

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.