Identifying Early Indicators of Breast Cancer Risk

The most commonly hypothesized model of breast cancer development posits an evolution through incremental steps of progressively increasing cellular abnormalities from normal epithelium through proliferative disease without atypia (PDWA), atypical hyperplasia, ductal carcinoma in situ, and then invasive breast cancer. This model is supported by epidemiologic studies that show a step-wise increase in relative risk (RR) of subsequent development of invasive breast cancer from PDWA (RR=2) to atypical hyperplasia (RR=4) to DCIS (RR=10).

To define the critical factors that influence whether a premalignant lesion will develop into invasive cancer, we are investigating an extensive cohort of patients with benign breast disease (BBD) that was assembled at the Mayo Clinic and for which subsequent cancer progression status is known. We are using transcriptional profiling and pathological observations to identify specific features that are most associated with progression to invasive cancer.

We are using this information, in combination with our animal and cell culture models, to develop novel approaches to target cancer-associated processes towards the ultimate goal of prevention of breast cancer formation.