PROJECT SUMMARY/ABSTRACT Overall age-adjusted mortality rates for female breast cancer have decreased significantly over the last 40 years (31.5/100,000 in 1979 to 20.6/100,000 in 2016), however breast cancer mortality rates for Black women are only slightly lower than they were in the 1970s (30.5/100,000 in 1979 vs. 27.3/100,000 in 2016). Reasons for these disparities are likely multifactorial, but differences in body composition that alter the tumor’s exposure to chemotherapy drugs may be one contributing factor. Traditionally, chemotherapy doses have been calculated using body surface area (BSA), which is calculated based on simple height and weight measurements. However, BSA does not account for differences in lean body mass (LBM) and adipose tissue (AT). Individuals with the same height and weight can have significantly different distributions of LBM and AT, which could contribute to variation in drug distribution, clearance, and drug-related toxicity. Data from several large population-based studies indicate that among women with similar body mass index, on average, non- Hispanic Blacks have a higher proportion of skeletal muscle and lower proportion of AT compared to non- Hispanic Whites. These differences in body composition could mean that use of standard chemotherapy dosages (established through clinical trials with often predominantly White participants) could result in many Black women receiving sub-optimal chemotherapy dosing per kg LBM, increasing the risk of failure to achieve remission, disease progression or recurrence. However, there are still key questions that need to be clarified before changes in drug dosing based on body composition can be evaluated in clinical trials, including which body composition metrics are associated with optimal treatment outcomes, and whether dosing should focus solely on LBM or also include measures of adiposity. To address our long-term goal of improving breast cancer treatment outcomes overall and eliminating disparities in outcomes for Black women, this retrospective study of 400 women who were treated for breast cancer (approximately 44% White and 45% Black) will use existing computed tomography scans to measure body composition and address the following specific aims: 1) determine the extent to which drug dose/kg LBM differs between White and Black women being treated with an anthracycline- or taxane-based chemotherapy regimen for invasive breast cancer, and 2) determine the extent to which drug dose/kg LBM and measures of abdominal AT are independently and jointly associated with chemotherapy toxicity and completion of scheduled treatment. Findings from the proposed study will contribute important foundational data on body composition among women with breast cancer, and how body composition may vary by race. If body composition measures are found to be associated with chemotherapy- related toxicity, drug dosing could be tailored to an individual’s body composition in order to maximize treatment effectiveness while minimizing treatment-related toxicity.

PROJECT NARRATIVE Tailoring chemotherapy dosing to a person’s body composition could be another tool in the precision medicine toolbox, allowing clinicians to maximize treatment effectiveness while minimizing treatment-related toxicity. This study will provide key preliminary data for future studies, including evaluation of the role of body composition in pharmacokinetics of chemotherapeutic agents, and simulation and prediction modeling to refine drug dosing recommendations.