Early Treatment Response Detection Using Highly Accurate and Reliable Breast Density Measure Derived from MRI

Abstract Breast cancer (BCa) is the most commonly diagnosed cancer and second most common cause of cancer death among women in the U.S. Breast density (BD) is a radiologic (image based) measure of the proportion of fat to fibroglandular tissues in the breast. It has been suggested that BD is an independent and significant risk factor for BCa, and BD changes have been increasingly incorporated as an intermediate surrogate endpoint to evaluate efficacy of drugs such as tamoxifen and aromatase inhibitors used in the treatment and prevention of BCa. Currently, mammography is the most widely used method of BD determination (MG-BD), but the requirement for ionizing radiation prohibits its use in studies requiring frequent monitoring. The accuracy of MG-BD is also limited due to the breast compression and the x-ray exposure calibration. As such, the accurate measurement of BD has emerged as a priority for assessing BCa risk and for evaluating the effects of prevention strategies aimed at reducing BD. BD derived from fat-water decomposition MRI (FWMRI-BD) has been proposed as an alternative for BD quantification without ionizing radiation. This proposal establishes an optimized FWMRI-BD measure that is automated, more accurate and reliable than the existing methods. Our immediate goal is to apply this highly sensitive FWMRI-BD change as a biomarker in research studies aimed at assessing the action of candidate prevention compounds on BD at an earlier time point than what is currently achievable using conventional mammography. In a previous study, a =10% decrease in MG-BD after 12–18 months of tamoxifen therapy was associated with clinical benefit. Thus, in the longer term, earlier detection of BD changes that ultimately correlate with reduced BCa or BCa relapse will offer a precision medicine strategy to encourage intervention adherence for responders and allow individualized dose modification for non-responders. In addition, it will also facilitate discovery of novel agents for potential BCa chemopreventives using smaller studies, shorter intervention periods and at considerably lower costs.