American College of Radiology Imaging Network Acrin 6702 a Multi-center Study Evaluating the Utility of Diffusion Weighted Imaging for Detection and Diagnosis of Breast Cancer

Magnetic resonance imaging (MRI) has become an important tool for breast imaging. Conventional breast MRI is highly sensitive for detecting cancer, but can also result in many false positives. Diffusion weighted imaging (DWI) can provide complementary information for lesion characterization by measuring the mobility of water molecules in tissue allowing an indirect assessment of tissue microstructure. Single center studies have shown promise for adding DWI to breast MR examinations to improve specificity; however, differences in study design have caused variable results and there is no consensus on the optimal approach. To determine the added value of DWI for reducing false positives of breast MRI, it is important to validate these findings in a multi-center study with DWI implemented across a variety of systems (manufacturers/models/magnet strengths). Furthermore, it is essential to use a standardized approach to breast DWI acquisition and analysis to identify optimal apparent diffusion coefficient (ADC) thresholds for discriminating benign from malignant breast lesions. For this study, we plan to evaluate DWI scans performed in women with breast lesions identified by conventional breast MRI. We will determine whether an ADC threshold can be defined for distinguishing benign and malignant lesions on DWI, assess the difference in ADC cutoffs for mass and non-mass lesions, and investigate the potential improvement in accuracy using techniques such as nonzero minimum b-value (to remove perfusion effects in the ADC measures) and normalized ADC measures (to account for variations in water content and other factors). The outcomes of this study are potentially significant because if results are positive and DWI is found to be valuable for distinguishing benign from malignant breast lesions, (1) DWI could be easily implemented into routine clinical breast MR examinations (including screening exams) to improve specificity and reduce the number of unnecessary biopsies while adding only a few minutes to the exam and requiring no additional contrast or hardware, (2) the study will answer essential questions for implementing breast DWI in the multi-center clinical setting, such as establishing optimal ADC cutoff values and developing standardized image acquisition, data quality assurance, and interpretation methodologies, and (3) the study will provide valuable preliminary data and methodology to support a larger prospective Phase 3 trial to validate the improvement in diagnostic performance achieved by incorporating DWI into conventional breast MRI assessments. A negative result of the study will indicate that this technology is not yet ready for incorporating into standard breast MRI assessments and more work must be done to address specific issues identified by the study. BACKGROUND AND SIGNIFICANCE Conventional Breast MRI Breast cancer is the second leading cause of cancer death among women in the United States, and earlier detection through screening is a fundamental way to improve survival. Dynamic contrast enhanced (DCE-MRI) of the breast has a high sensitivity for breast cancer detection and is the most sensitive technique for screening high-risk women and detecting contralateral or multifocal disease in patients with recently diagnosed breast cancer. However, overlap in the appearance of benign and malignant breast lesions on DCE-MRI can produce many false positives. In high-risk women, data from 9 studies have shown that MRI screening prompts a biopsy in approximately 7.8% of women, of which 40% are found to have