Ductal carcinoma in situ (DCIS) is an early, pre-invasive form of breast cancer that conveys an excellent prognosis if local control is achieved. However, because it is often difficult to appreciate the true extent of DCIS on mammography and clinical exam, DCIS is treated aggressively once detected, using surgery, radiation and hormonal treatment, with the goahof preventing disease progression. Yet, there is evidence that not all DCIS lesions will progress to invasive cancer. There is interest in finding better ways to assess DCIS and potentially identify those DCIS lesions that progress slowly to invasive cancer, or not at all. It is possible that such slowly progressing DCIS lesions could be treated non-surgically with therapies that prevent or reverse progression to invasive disease. The goal of this study is to improve our ability to measure DCIS using MR imaging techniques and to determine through histopathologic correlation the imaging characteristics associated with occult invasive disease and multi-centricity, both of which can change patient management if identified early. The primary aim is to refine existing contrast-enhanced (CE) MR methods that have already been tested for invasive carcinoma, to better identify DCIS and define its extent. We will also investigate two new techniques for their ability to characterize DCIS: high spectral spatial resolution imaging (HiSS) and diffusion-weighted imaging (DWI). HiSS and DWI will add information about DCIS related to tissue cellularity and subvoxelar fat and water spectral components, respectively, that may be complementary to the information about tumor angiogenesis provided by CE-MRI. The combination of imaging techniques will be applied to measure treatment- related changes in DCIS in response to hormonal and statin therapy. Two pilot clinical trials designed to investigate the feasibility of hormonal and statin treatment for DCIS are beginning at our institution and will enroll patients with biopsy-proven DCIS to receive short-term treatments prior to surgery. Patients will be evaluated using both imaging and tissue biomarkers to assess change with treatment (hormonal trial) and measure dose-related effects (statin trial). Both trials are intended to identify biomarkers that are sensitive to treatment change and can be used in subsequent larger trials to test non-surgical therapies for their ability to reduce the risk of DCIS progression to invasive cancer. The pilot trials afford an opportunity to refine MRI methods for DCIS and to improve their effectiveness for guiding patient selection and treatment assessment.
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