Characterizing the role of adolescent physical activity in early onset breast cancer risk for women across the familial risk continuum - PROJECT SUMMARY Early onset breast cancer (BC) incidence has increased dramatically worldwide, including in the U.S. where the greatest increase has occurred in young non-Hispanic Black (NHB) women. Identifying the modifiable causes of early onset BC is critical for reducing health inequities, a top priority for public health and BC prevention, and addresses one of the NCI’s 2020 provocative questions on the etiology of cancers in adults under age 40. Physical activity in adulthood is an established risk factor for cancer, and the long latency of tumorigenesis suggests that physical activity in adolescence may play an important role in the development of early onset BC. However, there is currently limited epidemiologic data, especially from racially diverse cohorts, to support this. It is essential that we address this major gap in the evidence-base. The overarching goal of this study is to elucidate the role of adolescent physical activity in the risk of and outcomes from early onset BC, including whether physical activity impacts breast tissue biomarkers in adolescent girls and young women. Aim 1 (K99) will evaluate adolescent physical activity in association with early onset BC risk and outcomes after diagnosis in young women across the continuum of BC susceptibility using survival modeling approaches coupled with causal methods, including Mendelian randomization and sibling set analyses. This aim will use existing data from a racially diverse family-based cohort of 31,640 women that is enriched for BC family history (BCFH) and includes 7,703 (1,422 NHB or Hispanic) women diagnosed with BC before age 50 (3,108 diagnosed before age 40). Aim 2 (K99) will determine if physical activity is associated with intermediate markers of BC risk in adolescent girls, including timing of breast development and breast tissue composition (BTC) measured by optical spectroscopy (OS). This aim will use existing prospective data from two adolescent cohorts, including a multiethnic cohort of 1,040 girls that is enriched for BCFH and a cohort of 216 NHB and Hispanic girls in NYC. Aim 3 (R00) will evaluate if adolescent physical activity is associated with structural and metabolic differences in the breast tissue of young women under age 40 and determine if these alterations are associated with early onset BC risk. This aim will be completed during the independent R00 phase by conducting a case-control study in 150 women under age 40, newly diagnosed with BC, and 300 matched controls (sample ≥50% NHB or Hispanic). BTC will be measured in cases and controls using OS and mammography. Taken together, this study will provide the most comprehensive evaluation of adolescent physical activity and early onset BC to date, which is needed to move the field of BC prevention research forward in developing novel intervention strategies for populations at increased risk of early onset disease. This research will be complemented by experiential and didactic training in molecular and genetic epidemiology, advanced statistical methods, physical activity research, and intervention design, as well as career development activities. This K99/R00 award will thus facilitate the long-term career objective of leading an independent research program studying modifiers of cancer risk that are amenable to early life intervention.
