Linda Vahdat, MD, MBA

Titles and Affiliations

Deputy Cancer Center Director,
Section Chief and Medical Oncology Member
Breast Medicine Service
Dartmouth Cancer Center

Research area

Improving the treatment of high-risk triple-negative breast cancer

Impact

Triple-negative breast cancer (TNBC) accounts for 15-20 percent of all breast cancers but makes up 50 percent of metastatic breast cancers. Patients who complete chemotherapy before surgery and have significant residual disease at the time of surgery, are at highest risk for relapse. The only treatment options for these patients are chemotherapy with the drug capecitabine and radiation. There is an urgent need to develop new treatment strategies for TNBC to reduce relapse and improve survival. Copper has been shown to play an integral role in the process of metastasis, both within tumor cells and in the tumor microenvironment. Dr. Vahdat is building on this finding and testing a novel copper-targeted treatment for TNBC. The therapeutic depletion of copper has the potential to enhance standard chemotherapy and prevent metastasis in patients with high-risk TNBC.

Progress Thus Far

Through a series of detailed investigations, Dr. Vahdat and her team found that reducing bioavailable copper disrupts the “seeding” of tumors to distant metastatic sites. This led them to examine the mechanisms involved: They conducted a clinical trial to test a copper depletion pill in patients at an extraordinarily high risk of tumor recurrence. Not only was the drug safe and well tolerated, but it could also alter tumor- and patient-related factors that promote metastasis thereby preventing it. It was particularly effective in TNBC. Further studies showed that the tumor microenvironment was altered, specifically disrupting how a tumor hijacks cellular architecture to metastasize.

What’s next

Dr. Vahdat is currently leading a clinical trial to test whether adding a copper depletion compound (tetrathiomolybdate) to standard treatments can prevent metastases in patients with TNBC and at a high-risk for relapse. This multicenter clinical trial is enrolling patients from several NCI designated Cancer Centers and testing standard chemotherapy with capecitabine versus capecitabine and tetrathiomolybdate.

Biography

Linda Vahdat, MD, MBA is a Breast Oncologist and Deputy Cancer Center Director at Dartmouth. Prior to her appointment in 2022, she was a senior member of the Breast Medicine Service at Memorial Sloan Kettering Cancer Center, Evelyn Lauder Breast Center. She earned her medical degree from Mount Sinai School of Medicine and MBA from Massachusetts Institute of Technology, Sloan School of Management. She has performed clinical and translational research in breast cancer for over 25 years with a focus on new therapies in patients with high risk of relapse and metastatic disease. Dr. Vahdat’s pioneering work in metals and their role in breast cancer has opened the door to new and innovative treatments for triple-negative breast cancer.

Over the course of 15 years, Dr. Vahdat directed and built an integrated Breast Cancer Research Program at Weill Cornell Medicine whose strategy was not only to treat breast cancer metastases, but to try to prevent them through novel drugs targeting minimal residual disease. Her particular research interest in triple-negative breast cancer led her to establish a clinic dedicated to the research and treatment of triple-negative breast cancer at Weill Cornell Medicine in January 2014. Her major research focus continues to understand the process of tumor metastases in breast cancer patients at high risk of relapse and to develop drugs to interrupt that process.