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Introduction: Lifetime estrogen exposure is an essential factor for breast carcinogenesis. While adiposity impacts circulating hormones throughout a woman's life, weight gain in adulthood appears to have paradoxical effects at premenopausal and postmenopausal breast cancer risk. Thus, we evaluated the association between weight change throughout distinct lifetime periods with breast cancer risk stratified by menopausal status. Methods: We conducted a prospective cohort study of 73,347 Korean women aged 40 to 69 years who were enrolled in the population-based Health Examines-Gem Study (HEXA, 2004-2013). Using anthropometry obtained from physical examination and self-reported weights at ages 18-20, 35 and 50 assessed through a validated questionnaire at enrollment, we calculated body mass index (BMI), absolute weight change and weight change per year for the following 5 age periods: entire adulthood (age 18-20 years to recruitment); early reproductive years (age 18-20 to age 35); middle adulthood (age 35 years to recruitment); late reproductive years (age 35 to 50); and peri-/postmenopausal years (since 50 years to recruitment). Restricted cubic spline model was constructed using three knots and Cox regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for breast cancer risk. Results: We identified 843 breast cancer cases over 758,116 person-years of follow-up (median 9.2 years). Postmenopausal women with BMI over 27.5kg/m2 at enrollment had a 48% (aHR 1.48, 95%CI 1.13-1.96; p-trend=0.03) increased risk of breast cancer. Women who gained 5 kg or more since age 35 had a 66% increased risk of premenopausal breast cancer (aHR 1.66, 95%CI 1.21-2.28; p-trend=0.03) compared to those who had stable weight (±2.5 kg), while those who gained 0.75 kg annually after the age of 50 had a 40% increased risk of postmenopausal breast cancer (aHR 1.41, 95%CI 1.01-1.96; p-trend=0.03). There was a non-linear relationship between annual average weight change in entire and middle adulthood and breast cancer risk (p < 0.01). The results remained unchanged after further adjusting for weight at each age. Conclusions: Our findings suggest that absolute weight gain from age 35 was associated with an increased risk of premenopausal breast cancer, while persistent weight gain from age 50 increased the risk of breast cancer in postmenopausal women. Furthermore, we confirmed that adiposity, assessed as body mass index, increases the risk of postmenopausal breast cancer in Korean women. Citation Format: Katherine De la Torre, Woo-Kyoung Shin, Hwi-Won Lee, Dan Huang, Sukhong Min, Aesun Shin, Jong-Koo Lee, Wonshik Han, Daehee Kang. Weight gain after age 35 increases the risk of breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3051. |
