Advancing new treatments and prediction strategies for patients with HER2-positive breast cancer brain metastasis. 

Impact

The spread of breast cancer to the brain has a significant impact on the quality of life and survival of patients withMBC and remains an urgent clinical problem, one that Dr. Lin has been focused on solving. She has led two significant clinical trials: testing the combination of the anti-HER2 drug (neratinib) and a chemotherpy agent (capecitabine) for patients with HER2-positive breast cancer that had spread to the brain; and testing the anti-HER2 drug tucatinib and trastuzumab (an immunotherapy drug) in these patients, establishing the intracranial efficacy of tucatinib. These clinical trials led to FDA-approval for both neratinib and tucatinib for treating HER2-positive breast cancer that has spread to the brain. Dr. Lin is now focused on assessing the genomic alterations that occur with the development of breast cancer related brain and central nervous system metastases. For these studies, her team utilizes the Ending Metastatic Breast Cancer for Everyone (EMBRACE) research study database which contains data from over 2,000 patients with MBC. In related studies, Dr. Lin and her colleagues are examining efficacy of antibody-drug conjugates (ADCs) for the treatment of central nervous system metastases. Both investigations will address the urgent need to find more effective treatments for both early-stage and metastatic HER2-positive breast cancer. 

Progress Thus Far

Dr. Lin has completed the genomic sequencing of 778 primary tumor samples in patients with MBC with known sites of metastatic involvement. For hormone receptor-positive breast cancers, she has observed distinct genomic differences in HER2-positive compared to HER2-negative tumors. Other studies, conducted in collaboration with fellow BCRF-investigator Dr. Jean Zhao, have demonstrated that the ADC trastuzumab deruxtecan (T-DXd/Enhertu®) has intracranial activity in laboratory models, providing a rational for testing these findings in a clinical trial to be launched soon. 

What's next

Dr. Lin and her colleagues will continue to analyze the genomic sequencing data to identify potential predictors of breast cancer-related development of brain or central nervous system metastases. Collaboration is ongoing with Dr. Zhao to develop preclinical models to test T-DXd and other agents. Dr. Lin expects to launch a prospective, multicenter clinical trial to test T-DXd in patients with progressive BC-BrM.