Damon Runyon Researchers

The development of HER2-targeted therapies over the past two decades has had tremendous positive impact on the lives of HER2-positive breast cancer patients. However, tumor resistance to these therapies remains a significant challenge: a sizable portion of patients with early-stage HER2-positive breast cancer develop recurrence, and the vast majority of patients with metastatic HER2-positive breast cancer eventually progress through treatment. Jennifer proposes to construct a model of HER2-positive breast cancer evolution that will reveal how the cancer changes over time when treated with HER2-targeted therapy. She will examine each tumor at multiple time points in the course of its treatment: at diagnosis, during initial treatment (with HER2-targeted therapy and/or chemotherapy), after completion of initial treatment, and at one or more sites of metastasis. To create this model, she will analyze multiple regions within each tumor and also test circulating DNA that the tumor sometimes sheds into the blood. She will also examine the specific changes present in the cells that develop resistance to HER2-targeted therapy. A deeper understanding of how tumors evolve under the pressure of treatment will open new avenues to optimizing treatment delivery. Markers of treatment resistance may further allow us to personalize therapy choices, delivering extra therapy to those patients who need it and sparing others unnecessary toxicity.