Grant Number:	5R00CA263024-05 Interpret this number
Primary Investigator:	Kehm, Rebecca
Organization:	Columbia University Health Sciences
Project Title:	Characterizing the Role of Adolescent Physical Activity in Early Onset Breast Cancer Risk for Women Across the Familial Risk Continuum
Fiscal Year:	2026

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 the growing burden of early onset disease, 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 a key role in the development of early onset BC. However, there is currently limited epidemiologic data to support this hypothesis. The overarching goal of this project is thus 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. In the K99 phase, we advanced this goal by generating some of the first data supporting that adolescent physical activity is associated with reduced BC risk before the age of 40 years, particularly if maintained in early adulthood. We also made advances in understanding the mechanisms through which physical activity reduces BC risk in early life, including through delayed onset of breast development, lower breast density in adolescence, and lower oxidative stress in adolescence. In the R00 phase, we will continue to build the evidence base linking physical activity across the life course to early onset BC risk and outcomes after diagnosis through the following specific aims. In Aim 1, we will further elucidate the role of physical activity in adolescence and early adulthood in early onset BC risk by conducting a case-control study in 200 women, recently diagnosed with BC before the age of 40 years, and 200 healthy controls aged 18-39 years and at increased familial risk for BC. This study will recruit from a family-based cohort in New York City and use a validated survey instrument to capture detailed physical activity histories, thus overcoming certain limitations of our first study on adolescent physical activity and early onset BC risk. In Aim 2, we will determine if physical activity (measured by accelerometers) is associated with breast tissue composition in healthy young women, under age 40 years and at increased risk for BC (controls from Aim 1). We will use optical spectroscopy to measure breast tissue composition and collect breast images from mammograms and magnetic resonance imaging. In Aim 3, we will examine the relationship between physical activity (measured by accelerometers) and health outcomes in young women recently diagnosed with BC (cases from Aim 1), including fatigue, health-related quality of life, and psychological conditions (depression, anxiety, stress). Taken together, this study will provide the most comprehensive evaluation of adolescent physical activity and early onset BC to date, which will move the field of BC prevention research forward in developing novel intervention strategies for populations at increased risk of early onset disease.