To investigate the association between metabolic syndrome (MetS) and risk of breast cancer mortality by menopausal status, obesity, and subtype.
Data from 94,555 women free of cancer at baseline in the National Institute of Health-American Association of Retired Persons Diet and Health Study cohort (NIH-AARP) were used to investigate the prospective associations of baseline MetS and components with risk of breast cancer mortality using Cox proportional hazard regression models adjusted for baseline behavioral and demographic covariates.
During a mean follow-up duration of 14 years, 607 women in the cohort died of breast cancer. Overall, MetS was associated with a 73% increased risk of breast cancer mortality (HR 1.73; 95% CI 1.09–2.75); the association remained significant among post-menopausal women overall (HR 2.07, 95% CI 1.32, 3.25), and among those with overweight/obesity (HR 1.15, 95% CI 0.81, 1.64). MetS was associated with increased risk of breast cancer mortality for ER+/PR+ (HR 1.28, 95% CI 0.52, 3.16) and lower risk for ER−/PR− (HR 0.44, 95% CI 0.11, 1.75) subtypes; however, the associations were not statistically significant. Of the individual MetS components, high waist circumference (HR 1.32, 95% CI 1.03, 1.70), high cholesterol (HR 1.24, 95% CI 1.05, 1.46), and hypertension (HR 1.24, 95% CI 1.05, 1.46) were independently associated with increased risk of breast cancer mortality.
MetS was associated with increased risk of breast cancer mortality, especially among post-menopausal women. Further studies with larger sample sizes are needed to definitively determine the extent to which these associations vary by breast cancer subtype.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
The NIH-AARP dataset is publicly available for research investigations upon submission and approval of a research proposal. Details can be found at https://www.nihaarpstars.com.
Nilsson PM, Engstrom G, Hedblad B (2007) The metabolic syndrome and incidence of cardiovascular disease in non-diabetic subjects—a population-based study comparing three different definitions. Diabet Med 24(5):464–472
Athyros VG, Ganotakis ES, Elisaf MS, Liberopoulos EN, Goudevenos IA, Karagiannis A, Group G-MC (2007) Prevalence of vascular disease in metabolic syndrome using three proposed definitions. Int J Cardiol 117(2):204–210
Koren-Morag N, Goldbourt U, Tanne D (2005) Relation between the metabolic syndrome and ischemic stroke or transient ischemic attack: a prospective cohort study in patients with atherosclerotic cardiovascular disease. Stroke 36(7):1366–1371
Grundy SM (2008) Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 28(4):629–636
Abrahamson PE, Gammon MD, Lund MJ, Flagg EW, Porter PL, Stevens J, Swanson CA, Brinton LA, Eley JW, Coates RJ (2006) General and abdominal obesity and survival among young women with breast cancer. Cancer Epidemiol Biomark Prev 15(10):1871–1877
Chen H-l, Ding A, Wang M-l (2016) Impact of central obesity on prognostic outcome of triple negative breast cancer in Chinese women. SpringerPlus 5(1):594
Ogundiran TO, Huo D, Adenipekun A, Campbell O, Oyesegun R, Akang E, Adebamowo C, Olopade OI (2012) Body fat distribution and breast cancer risk: findings from the Nigerian breast cancer study. Cancer Causes Control 23(4):565–574
Nicolucci A (2010) Epidemiological aspects of neoplasms in diabetes. Acta Diabetol 47(2):87–95
Pereira A, Garmendia ML, Alvarado ME, Albala C (2012) Hypertension and the risk of breast cancer in Chilean women: a case-control study. Asian Pac J Cancer Prev 13(11):5829–5834
Soler M, Chatenoud L, Negri E, Parazzini F, Franceschi S, la Vecchia C (1999) Hypertension and hormone-related neoplasms in women. Hypertension 34(2):320–325
Calip GS, Malone KE, Gralow JR, Stergachis A, Hubbard RA, Boudreau DM (2014) Metabolic syndrome and outcomes following early-stage breast cancer. Breast Cancer Res Treat 148(2):363–377
Berrino F, Villarini A, Traina A, Bonanni B, Panico S, Mano MP, Mercandino A, Galasso R, Barbero M, Simeoni M et al (2014) Metabolic syndrome and breast cancer prognosis. Breast Cancer Res Treat 147(1):159–165
Maiti B, Kundranda MN, Spiro TP, Daw HA (2010) The association of metabolic syndrome with triple-negative breast cancer. Breast Cancer Res Treat 121(2):479–483
Healy LA, Ryan AM, Carroll P, Ennis D, Crowley V, Boyle T, Kennedy MJ, Connolly E, Reynolds JV (2010) Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer. Clin Oncol (R Coll Radiol) 22(4):281–288
Bjorge T, Lukanova A, Jonsson H, Tretli S, Ulmer H, Manjer J, Stocks T, Selmer R, Nagel G, Almquist M et al (2010) Metabolic syndrome and breast cancer in the me-can (metabolic syndrome and cancer) project. Cancer Epidemiol Biomark Prev 19(7):1737–1745
Emaus A, Veierod MB, Tretli S, Finstad SE, Selmer R, Furberg AS, Bernstein L, Schlichting E, Thune I (2010) Metabolic profile, physical activity, and mortality in breast cancer patients. Breast Cancer Res Treat 121(3):651–660
Simon MS, Beebe-Dimmer JL, Hastert TA, Manson JE, Cespedes Feliciano EM, Neuhouser ML, Ho GYF, Freudenheim JL, Strickler H, Ruterbusch J et al (2018) Cardiometabolic risk factors and survival after breast cancer in the Women’s Health Initiative. Cancer 124(8):1798–1807
Gathirua-Mwangi WG, Song Y, Monahan PO, Champion VL, Zollinger TW (2018) Associations of metabolic syndrome and C-reactive protein with mortality from total cancer, obesity-linked cancers and breast cancer among women in NHANES III. Int J Cancer 143(3):535–542
Phipps AI, Malone KE, Porter PL, Daling JR, Li CI (2008) Reproductive and hormonal risk factors for postmenopausal luminal, HER2-overexpressing, and triple-negative breast cancer. Cancer 113(7):1521–1526
Fan Y, Ding X, Wang J, Ma F, Yuan P, Li Q, Zhang P, Xu B (2015) Decreased serum HDL at initial diagnosis correlates with worse outcomes for triple-negative breast cancer but not non-TNBCs. Int J Biol Mark 30(2):e200–e207
Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status–a meta-analysis. Int J Cancer 124(3):698–712
Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, Navarro Rosenblatt D, Thune I, Vieira R, Norat T (2014) Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 25(10):1901–1914
Chan DS, Norat T (2015) Obesity and breast cancer: not only a risk factor of the disease. Curr Treat Options Oncol 16(5):22
Schatzkin A, Subar AF, Thompson FE, Harlan LC, Tangrea J, Hollenbeck AR, Hurwitz PE, Coyle L, Schussler N, Michaud DS et al (2001) Design and serendipity in establishing a large cohort with wide dietary intake distributions: the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Am J Epidemiol 154(12):1119–1125
Etemadi A, Sinha R, Ward MH, Graubard BI, Inoue-Choi M, Dawsey SM, Abnet CC (2017) Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ 357.j1957
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16):1640–1645
Park Y, Leitzmann MF, Subar AF, Hollenbeck A, Schatzkin A (2009) Dairy food, calcium, and risk of cancer in the NIH-AARP diet and health study. Arch Intern Med 169(4):391–401
Hiller L, Marshall A, Dunn J (2015) Assessing violations of the proportional hazards assumption in Cox regression: does the chosen method matter? Trials 16(Suppl 2):P134–P134
Rong SS, Chen LJ, Leung CKS, Matsushita K, Jia L, Miki A, Chiang SWY, Tam POS, Hashida N, Young AL et al (2016) Ethnic specific association of the CAV1/CAV2 locus with primary open-angle glaucoma. Sci Rep 6:27837
Monzavi-Karbassi B, Gentry R, Kaur V, Siegel ER, Jousheghany F, Medarametla S, Fuhrman BJ, Safar AM, Hutchins LF, Kieber-Emmons T (2016) Pre-diagnosis blood glucose and prognosis in women with breast cancer. Cancer Metab 4:7
Bandera EV, Maskarinec G, Romieu I, John EM (2015) Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective. Adv Nutr 6(6):803–819
Borugian MJ, Sheps SB, Kim-Sing C, Olivotto IA, Van Patten C, Dunn BP, Coldman AJ, Potter JD, Gallagher RP, Hislop TG (2003) Waist-to-hip ratio and breast cancer mortality. Am J Epidemiol 158(10):963–968
Zhang M, Cai H, Bao P, Xu W, Qin G, Shu XO, Zheng Y (2017) Body mass index, waist-to-hip ratio and late outcomes: a report from the Shanghai Breast Cancer Survival Study. Sci Rep 7:6996
Kang S, Song J, Kang H, Kim S, Lee Y, Park D (2003) Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells. Eur J Endocrinol 148(1):147–155
Djiogue S,Nwabo, Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, Seke Etet PF (2013) Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer 20(1):R1–R17
Chumsri S, Howes T, Bao T, Sabnis G, Brodie A (2011) Aromatase, aromatase inhibitors, and breast cancer. J Steroid Biochem Mol Biol 125(1–2):13–22
Subbaramaiah K, Howe LR, Bhardwaj P, Du B, Gravaghi C, Yantiss RK, Zhou XK, Blaho VA, Hla T, Yang P et al (2011) Obesity is associated with inflammation and elevated aromatase expression in the mouse mammary gland. Cancer Prev Res 4(3):329–346
Lorincz AM, Sukumar S (2006) Molecular links between obesity and breast cancer. Endocr Relat Cancer 13(2):279–292
Lobo RA (2008) Metabolic syndrome after menopause and the role of hormones. Maturitas 60(1):10–18
Carr MC (2003) The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 88(6):2404–2411
Monteiro R, Azevedo I (2010) Chronic inflammation in obesity and the metabolic syndrome. Mediat Inflamm 289645
Hsu M-C, Lee K-T, Hsiao W-C, Wu C-H, Sun H-Y, Lin I-L, Young K-C (2013) The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study. BMC Cancer 13(1):330
Chen SB, Lee YC, Ser KH, Chen JC, Chen SC, Hsieh HF, Lee WJ (2009) Serum C-reactive protein and white blood cell count in morbidly obese surgical patients. Obes Surg 19(4):461–466
Allin KH, Nordestgaard BG, Flyger H, Bojesen SE (2011) Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study. Breast Cancer Res 13(3):R55
Villaseñor A, Flatt SW, Marinac C, Natarajan L, Pierce JP, Patterson RE (2013) Postdiagnosis C-reactive protein and breast cancer survivorship: findings from the WHEL study. Cancer Epidemiol Biomark Prev
Zhou P, Li B, Liu B, Chen T, Xiao J (2018) Prognostic role of serum total cholesterol and high-density lipoprotein cholesterol in cancer survivors: a systematic review and meta-analysis. Clin Chim Acta 477:94–104
Jeon JH, Kim SK, Kim HJ, Chang J, Ahn CM, Chang YS (2010) Lipid raft modulation inhibits NSCLC cell migration through delocalization of the focal adhesion complex. Lung Cancer 69(2):165–171
Reverter M, Rentero C, Garcia-Melero A, Hoque M,Vilà, de Muga S, Álvarez-Guaita A, Conway JRW, Wood P, Cairns R, Lykopoulou L et al (2014) Cholesterol regulates syntaxin 6 trafficking at trans-golgi network endosomal boundaries. Cell Rep 7(3):883–897
Hermansen SW, Leitzmann MF, Schatzkin A (2009) The impact on National Death Index ascertainment of limiting submissions to Social Security Administration Death Master File Matches in epidemiologic studies of mortality. Am J Epidemiol 169(7):901–908
We thank the participants in the NIH-AARP Diet and Health Study for their cooperation, and David Campbell and Jane Wang at Information management Services (Silver Spring, MD) for data support.
TA was funded by Grant K01TW010271 by the NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Conflict of interest
The authors declare no conflict of interest.
The Special Studies Institutional Review Board (IRB) of the U.S. National Cancer Institute approved the NIH-AARP Diet and Health Study (Protocol Number: OH95CN025).
About this article
Cite this article
Dibaba, D.T., Ogunsina, K., Braithwaite, D. et al. Metabolic syndrome and risk of breast cancer mortality by menopause, obesity, and subtype. Breast Cancer Res Treat 174, 209–218 (2019). https://doi.org/10.1007/s10549-018-5056-8
- Metabolic syndrome
- Breast cancer mortality
- Hormone-receptor subtypes