Ductal carcinoma in situ (DCIS) is a non-invasive tumor lesion of the breast that can advance to become invasive breast cancer (IBC). We do not understand how these lesions progress, nor can we identify which lesions will behave aggressively and progress to invasive cancer. Our research seeks to bridge these knowledge gaps by studying the relationship between DCIS tumor cells and their neighboring non-tumor cells (“stroma”), to better understand how the stroma promotes aggressive disease. Using patient samples and mouse models, we will evaluate tumor-stroma relationships in both early-stage and advanced breast cancer. We will evaluate stromal cells at the single-cell level to document how t...

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Ductal carcinoma in situ (DCIS) is a non-invasive tumor lesion of the breast that can advance to become invasive breast cancer (IBC). We do not understand how these lesions progress, nor can we identify which lesions will behave aggressively and progress to invasive cancer. Our research seeks to bridge these knowledge gaps by studying the relationship between DCIS tumor cells and their neighboring non-tumor cells (“stroma”), to better understand how the stroma promotes aggressive disease. Using patient samples and mouse models, we will evaluate tumor-stroma relationships in both early-stage and advanced breast cancer. We will evaluate stromal cells at the single-cell level to document how they evolve as breast cancer becomes more invasive. Novel single-cell technologies will reveal features of DCIS that were previously undetectable. We will also measure the effect of the stroma on the behavior of tumor cells, with particular focus on the relationship between tumor cells and immune cells. In fact, we previously observed that advanced breast cancer but not DCIS, is infiltrated by neutrophils and myeloid derived suppressor cells (MDSCs), immune cell types that may alter the normal anti-tumor function of immune cells. We will test the idea that MDSCs promote invasiveness by measuring their effect on tumor cells, and then determine if inhibiting MDSCs in our mouse model can prevent DCIS from becoming invasive. Our research will lead to a vastly improved understanding of the influence of the stroma on DCIS and its progression to invasive cancer. By understanding DCIS behavior, we will be better able to stratify DCIS as benign or aggressive. In addition, our studies will identify new tumor-stroma relationships that, if disrupted, may halt the advancement or recurrence of DCIS. Ultimately, we will be able to identify patients most at risk for recurrence of their breast lesion, and treat and eliminate these aggressive lesions before they can advance to deadly disease.

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