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Study Purpose: The incidence of breast cancer (BC) in young women under age 40 years has increased substantially over time, underscoring the need for a better understanding of early life modifiers of risk. We examined the association of recreational physical activity (RPA) with BC risk before age 40 years, focusing on RPA during the adolescent window of susceptibility. Methods: We used data from the ProF-SC Study, which is enriched for young women at increased risk for BC. We conducted an ambidirectional cohort analysis that included women, aged = 55 years at baseline, who were enrolled within 5 years of their first primary BC diagnosis or had no history of BC at baseline (n = 14,865). Women reported by baseline questionnaire their average levels of moderate and strenuous RPA during adolescence (12-17 years), which we converted to total metabolic equivalents per week (METs-per-week) and categorized into quartiles after adjusting for baseline age. We conducted attained age analyses until 40 years using multivariable Cox proportional hazards regression models adjusted for baseline sociodemographic and lifestyle factors. Follow-up started at age 18 years and ended at age at first invasive BC diagnosis, last follow-up, or 40 years, whichever came first. Results: There were 1,646 BC diagnoses before age 40 during 30,5594 person-years of follow-up. Being in the highest vs. lowest quartile of adolescent RPA was significantly associated with a 16% reduced risk of BC until age 40 before adjustment for baseline RPA (HR = 0.84, 95% CI = 0.73-0.97). This association was attenuated and no longer statistically significant after adjustment for baseline RPA (HR = 0.89, 95% CI = 0.77-1.04). We identified a statistically significant multiplicative interaction between adolescent and baseline RPA (interaction P value = 0.03). A one standard deviation increase in METs-per-week of baseline RPA was associated with a 5% reduced BC risk for women in the 10th percentile of adolescent RPA (HR = 0.95, 95% CI = 0.90-1.00) and an 11% reduced risk in the 90th percentile (HR = 0.89, 95% CI = 0.84-0.95). Conclusions: These findings suggest that adolescent physical activity might reduce breast cancer risk in young women and underscore the importance of maintain or increasing RPA levels across the lifecourse. [ABSTRACT FROM AUTHOR]

Early-life body size has been consistently associated with breast cancer risk. The direction of the association changes over time, with high birth weight, smaller adolescent body size, and adult weight gain all increasing breast cancer risk. There is also a clear positive association between larger body size and increased breast adipose tissue measured by mammograms, but less is known about how body size changes across life stages affect stromal and epithelial breast tissue. Using breast tissue slides from women with benign breast disease, Oh and colleagues applied machine learning methods to evaluate body size across the life course and adipose, epithelial, and stromal tissue concentrations in adulthood. They found consistent patterns for higher adipose and lower stromal tissue concentrations with larger childhood and adult body size at age 18 years. They reported lower levels of epithelial tissue with larger body size at 18 years, but not at other time periods. Additional studies examining how body size at different life stages may affect breast tissue composition will be important. Noninvasive methods that can provide measures of breast tissue composition may offer potential ways forward to ensure generalizability, and repeated measurements by life stage. See related article by Oh et al., p. 608 ., (©2021 American Association for Cancer Research.)