体重指数与绝经年龄前后的乳腺癌风险
BMI and breast cancer risk around age at menopause.
作者信息
Von Holle Ann, Adami Hans-Olov, Baglietto Laura, Berrington de Gonzalez Amy, Bertrand Kimberly A, Blot William, Chen Yu, DeHart Jessica Clague, Dossus Laure, Eliassen A Heather, Fournier Agnes, Garcia-Closas Montse, Giles Graham, Guevara Marcela, Hankinson Susan E, Heath Alicia, Jones Michael E, Joshu Corinne E, Kaaks Rudolf, Kirsh Victoria A, Kitahara Cari M, Koh Woon-Puay, Linet Martha S, Park Hannah Lui, Masala Giovanna, Mellemkjaer Lene, Milne Roger L, O'Brien Katie M, Palmer Julie R, Riboli Elio, Rohan Thomas E, Shrubsole Martha J, Sund Malin, Tamimi Rulla, Tin Tin Sandar, Visvanathan Kala, Vermeulen Roel Ch, Weiderpass Elisabete, Willett Walter C, Yuan Jian-Min, Zeleniuch-Jacquotte Anne, Nichols Hazel B, Sandler Dale P, Swerdlow Anthony J, Schoemaker Minouk J, Weinberg Clarice R
机构信息
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinksa Institutet, Stockholm, Sweden.
出版信息
Cancer Epidemiol. 2024 Apr;89:102545. doi: 10.1016/j.canep.2024.102545. Epub 2024 Feb 19.
BACKGROUND
A high body mass index (BMI, kg/m) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology.
METHODS
We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy.
RESULTS
The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO.
CONCLUSION
The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.
背景
高体重指数（BMI，kg/m²）与绝经前患乳腺癌风险降低相关，但与绝经后患癌风险增加有关。这种风险变化与绝经的具体时间关系尚不清楚。确定这一变化点有助于深入了解肥胖在乳腺癌病因学中的作用。
方法
我们在绝经前乳腺癌协作组中研究了BMI与乳腺癌风险之间的关联，研究对象年龄从45岁起，直至乳腺癌诊断、失访、死亡或55岁，以先到者为准。分析纳入了16项前瞻性研究中的609880名女性，其中9956名在55岁之前患乳腺癌。我们在年龄-时间上拟合了三种BMI风险比（HR）模型：常数模型、线性模型或非线性模型（通过样条函数），应用分段指数相加混合模型，以年龄作为主要时间尺度。我们将人时分为四个层次：绝经前；自然绝经后的绝经后阶段；因卵巢功能干预性丧失（双侧卵巢切除术（BO）或化疗）后的绝经后阶段；因子宫切除术但未行BO后的绝经后阶段。敏感性分析包括按成年早期的BMI分层，或排除使用绝经激素治疗的女性。
结果
常数BMI HR模型对所有四个绝经状态组的拟合效果最佳。在此模型下，BMI每增加五个单位与乳腺癌风险之间的估计关联为：绝经前HR = 0.87（95% CI：0.85，0.89），自然绝经后HR = 1.00（95% CI：0.96，1.04），卵巢功能干预性丧失后HR = 0.99（95% CI：0.93，1.05），子宫切除术但未行BO后HR = （95% CI：0.76，1.02）。
结论
在45 - 55岁年龄范围内，BMI与乳腺癌的HR值仍小于或接近1，这表明BMI与风险之间的正向关联在55岁之后才出现。
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