Leveraging the Healthy Oregon Project (HOP) to evaluate environmental exposures during critical reproductive periods and young-onset breast cancer risk

Background: Young-onset breast cancer (YOBC), diagnosed before age 50, has twice the mortality of cases diagnosed ≥50. In the US, YOBC diagnoses increased by 1.4% annually from 2012-2021, with higher increases in non-metropolitan vs. metropolitan areas in western states. Geographic disparities may be influenced by environmental factors, such as neighborhood socioeconomic context, limited healthcare access, and exposure to environmental hazards (e.g., pesticides, per- and polyfluoroalkyl substances [PFAS]-contaminated water, wildfire smoke), which have been associated with breast tissue inflammation and increased breast cancer risk. Shifts in critical reproductive periods (e.g., menarche, delayed childbirth, menopause) and parity or nulliparity, which may be shaped by these environmental factors, may also affect risk and interact synergistically with environmental stressors. Our objective was to assess environmental exposures during critical reproductive periods to evaluate YOBC risk in a western US state with strong urban-rural environmental exposure contrasts. Methods: We used the Healthy Oregon Project (HOP) - a statewide prospective cohort of >50,000 Oregonians - to assess rurality of residential addresses of enrolled females, 18-49 years old, diagnosed with YOBC. Cases were identified via self-report on the HOP baseline questionnaire. Baseline residential addresses were linked to the USDA Economic Research Service's Rural Urban Commuting Area (RUCA) codes, and classified as Urban (codes 1-3), Rural (codes 4-9), or Frontier (code 10). A supplementary reproductive lifecourse questionnaire, including residential addresses during critical reproductive windows, is in development to allow us to link spatial datasets (e.g., fine particulate air pollution [PM 2.5 ], wildfire smoke, temperature, PFAS in water, land cover, agricultural pesticides) to YOBC cases and matched controls. Results: HOP has consented 51,978 Oregonians (~1.5% of the state's 3.4 million adult residents). On baseline questionnaires, 37,695 (72.5%) identified as female at birth, and 615 reported a YOBC diagnosis. Overall, participants resided in Urban (72.5%), Rural (13.5%) and Frontier (1.9%) areas, with 12.1% missing. Those diagnosed with YOBC showed a similar distribution (79.8%, 13.5% and 2.3%, respectively; 4.4% missing). Conclusion: Rurality of HOP participants' residences was similar across those with YOBC and the overall cohort; this distribution is representative of Oregon's urban-rural composition. Future analyses will link historic residential addresses during critical reproductive windows across the lifecourse to spatiotemporally aligned environmental and socioeconomic exposure data to evaluate how cumulative, and potentially synergistic, environmental exposures contribute to YOBC risk.