Identifying the specific pathways and genes responsible for drug resistance and breast cancer recurrence to develop prevention strategies. 

Impact

Despite advances in detection and treatment, up to 30 percent of patients will experience a breast cancer recurrence with metastatic disease over their lifetimes, sometimes many years after treatment of their primary cancer. Two factors, the presence of residual disease and tumor cell dormancy—a phenomenon whereby tumor cells lay dormant and are undetectable—are likely responsible for many breast cancer recurrences. The mechanisms underlying these processes, however, are largely unknown. Dr. Chodosh is working to identify interventions for breast cancer survivors that can reduce the risk of recurrence and improve long-term outcomes. In his current BCRF research, he is exploring the biological underpinnings of the effects of obesity, weight loss, and exercise on breast cancer recurrence. Dr. Chodosh’s team developed novel laboratory models that recapitulate the effects of obesity, exercise, and caloric restriction on both residual cancer and tumor-cell dormancy. Using these models, they showed that a high-fat diet promoted the survival of disseminated and dormant tumor cells. His team is evaluating the mechanisms involved and hopes their findings will enable the design of behavioral and therapeutic interventions with the potential to prevent tumor recurrence and reduce the mortality associated with metastatic breast cancer. 

Progress Thus Far

Using his novel experimental models, Dr. Chodosh’s team has identified five classes of genes that may play a functional role in tumor cell dormancy and breast cancer recurrence. Other studies comparing the genomic data from patient-matched primary and recurrent metastatic breast cancers revealed that five genes were mutated in the metastases but not in the primary cancers. In the last year, Dr. Chodosh’s team developed a breast cancer model demonstrating that obesity can accelerate tumor recurrence and also found that these effects can be reversed by weight loss.  

What’s next

Dr. Chodosh and his team will test the role of the candidate genes that they identified in tumor dormancy and recurrence. They will also investigate the role of the candidate genes in the development of resistance to therapy and will continue experiments to determine the molecular and cellular basis for the impact of obesity on breast cancer recurrence. Improving our understanding of tumor dormancy and recurrence and developing therapies that specifically target dormant residual cancer cells is a critical step toward reducing breast cancer mortality.