既往研究结果表明，年轻时体重与绝经前乳腺癌风险成反比。不过，中年体重变化对于绝经前乳腺癌风险的影响尚不明确。
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2020年2月3日，国际抗癌联盟《国际癌症杂志》在线发表英国伦敦大学癌症研究院、牛津大学、伦敦帝国学院、美国国家卫生研究院、国家环境卫生科学研究所、国家癌症研究所、希望之城国家医疗中心、波士顿大学、纽约大学、霍普金斯大学、西德尼·金梅尔综合癌症中心、哈佛大学、布莱根医院和波士顿妇女医院、麻省大学、爱因斯坦医学院、南加利福尼亚大学、北卡罗来纳大学、瑞典卡罗林学院、于默奥大学、乌普萨拉大学、挪威奥斯陆大学、特罗姆瑟大学、挪威北极圈大学、挪威癌症登记中心、意大利比萨大学、都灵大学、世界卫生组织国际癌症研究机构、澳大利亚维多利亚抗癌协会、墨尔本大学、德国癌症研究中心、加拿大安大略癌症研究所、日本广岛放射线影响研究基金会、希腊卫生基金会的研究报告，对62万8463例成年女性体重变化与绝经前乳腺癌风险进行了前瞻调查数据汇总分析。
该研究对绝经前乳腺癌研究协作组17项前瞻研究的62万8463例女性个体数据进行汇总，对18～24岁时的初始体重、体重变化时间、其他乳腺癌风险因素、乳腺癌亚型进行分层之后，分析体重变化与绝经前乳腺癌风险之间的关系。通过多因素比例风险回归模型，计算风险比和95%置信区间。
结果，其中1万0886例女性绝经前被诊断出乳腺癌。
与18～24岁时的初始体重相比：
25～34岁时的体重每增加5公斤
乳腺癌风险相似
雌激素受体阳性乳腺癌风险相似（风险比：0.98，95%置信区间：0.95～1.01）
雌激素受体阴性乳腺癌风险相似（风险比：1.01，95%置信区间：0.96～1.07）
35～44岁时的体重每增加5公斤
乳腺癌风险低3%（风险比：0.97，95%置信区间：0.96～0.98）
雌激素受体阳性乳腺癌风险低5%（风险比：0.95，95%置信区间：0.93～0.97）
雌激素受体阴性乳腺癌风险相似（风险比：1.01，95%置信区间：0.98～1.04）
45～54岁时的体重每增加5公斤
乳腺癌风险低4%（风险比：0.96，95%置信区间：0.95～0.98）
雌激素受体阳性乳腺癌风险低4%（风险比：0.96，95%置信区间：0.94～0.98）
雌激素受体阴性乳腺癌风险相似（风险比：0.99，95%置信区间：0.95～1.02）
25～34岁之后，体重增加仅与雌激素受体阳性乳腺癌风险成反比，与雌激素受体阴性乳腺癌风险无显著相关性。
35～44岁之后，体重增加与乳腺癌风险无显著相关性。
对初始体重进行校正之后，体重减轻与乳腺癌风险或雌激素受体相关乳腺癌风险无显著相关性。
因此，该研究结果表明，无论成年前体重如何，中年女性绝经前体重与雌激素受体阳性乳腺癌风险成反比，与雌激素受体阴性乳腺癌风险无显著相关性，故有必要对这两种因素的生物学机制开展进一步研究。
Int J Cancer. 2020 Feb 3. [Epub ahead of print]
Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.
Schoemaker MJ, Nichols HB, Wright LB, Brook MN, Jones ME, O'Brien KM, Adami HO, Baglietto L, Bernstein L, Bertrand KA, Boutron-Ruault MC, Chen Y, Connor AE, Dossus L, Eliassen AH, Giles GG, Gram IT, Hankinson SE, Kaaks R, Key TJ, Kirsh VA, Kitahara CM, Larsson SC, Linet M, Ma H, Milne RL, Ozasa K, Palmer JR, Riboli E, Rohan TE, Sacerdote C, Sadakane A, Sund M, Tamimi RM, Trichopoulou A, Ursin G, Visvanathan K, Weiderpass E, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Sandler DP, Swerdlow AJ.
The Institute of Cancer Research, London, United Kingdom; National Institute of Environmental Health Sciences, National Institutes of Health, Durham, USA; Karolinska Institutet, Stockholm, Sweden; University of Oslo, Oslo, Norway; University of Pisa, Pisa, Italy; Beckman Research Institute of City of Hope, Duarte, USA; Slone Epidemiology Center at Boston University, Boston, USA; New York University School of Medicine, New York, USA; Johns Hopkins Bloomberg School of Public Health, Baltimore, USA; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, USA; International Agency for Research on Cancer, Lyon, France; Harvard T.H. Chan School of Public Health, Boston, USA; Brigham and Women's Hospital and Harvard Medical School, Boston, USA; Cancer Council Victoria, Melbourne, Victoria, Australia; The University of Melbourne, Melbourne, Victoria, Australia; University of Tromso, The Arctic University of Norway, Tromso, Norway; University of Massachusetts, Amherst, USA; DKFZ, Heidelberg, Germany; University of Oxford, Oxford, United Kingdom; Ontario Institute for Cancer Research, Toronto, Canada; National Cancer Institute, Bethesda, USA; Radiation Effects Research Foundation, Hiroshima, Japan; Imperial College, London, United Kingdom; Albert Einstein College of Medicine, New York, USA; Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Italy; Umea University, Umea, Sweden; Hellenic Health Foundation, Athens, Greece; Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; University of Southern California, Los Angeles, USA; Johns Hopkins School of Medicine, Baltimore, USA; International Agency for Research on Cancer, World Health Organization, Lyon, France; Uppsala University, Uppsala, Sweden; University of North Carolina Gillings School of Global Public Health, Chapel Hill, USA.
Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors, and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g. HR per 5kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
KEYWORDS: breast neoplasms; premenopause; body weight changes; risk factors; cohort studies
DOI: 10.1002/ijc.32892
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