title: The association between metabolic health, obesity phenotype and the risk of breast cancer.
abstract: Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (≥88 cm); elevated blood pressure (≥130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol-lowering medication use. During follow-up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m2with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m2and ≥1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR = 1.26, 95% CI: 1.01-1.56), as did women with a BMI ≥25 kg/m2and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR = 1.24, 95% CI: 0.99-1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ≥88 cm, waist circumference ≥80 cm, and waist-hip ratio ≥0.85 of 1.58, 95% CI: 1.02-2.46; 1.38, 95% CI: 1.09-1.75; and 1.38, 95% CI: 1.02-1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR = 0.71, 95% CI: 0.52-0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Yong-Moon Mark
authors.identifier: 0000-0002-5879-6879
authors.initials: YM
authors.lastname: Park
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: White
authors.affiliation: Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
authors.forename: Hazel B
authors.initials: HB
authors.lastname: Nichols
authors.affiliation: Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: O'Brien
authors.affiliation: Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Clarice R
authors.initials: CR
authors.lastname: Weinberg
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D012307:Risk Factors; D055105:Waist Circumference; D049629:Waist-Hip Ratio
keywords: metabolic health; metabolically healthy obese; metabolically unhealthy normal weight; normal weight central obesity; obesity; postmenopausal breast cancer