Abstract
We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants’ waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.
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References
American Cancer Society (2014) Cancer facts & figures 2014. American Cancer Society, Atlanta
Altekruse S, Kosary C, Krapcho M, Neyman N, Aminou R, Waldron W et al (eds) (2010) SEER cancer statistics review, 1975–2007. National Cancer Institute, Bethesda
American Cancer Society (2009) Breast cancer facts and figures 2009–2010. American Cancer Society, Atlanta
Demark-Wahnefried W, Platz EA, Ligibel JA, Blair CK, Courneya KS, Meyerhardt J et al (2012) The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomark Prev 21(8):1244–1259. doi:10.1158/1055-9965.epi-12-0485
Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A et al (2014) Body mass index and survival in women with breast cancer–systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol. doi:10.1093/annonc/mdu042
Snijder M, van Dam R, Visser M, Seidell J (2006) What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol 35(1):83–92. doi:10.1093/ije/dyi253
World Health Organization (2008) Waist circumference and waist–hip ratio. Report of a WHO expert consultation. World Health Organization, Geneva
Cerhan JR, Moore SC, Jacobs EJ, Kitahara CM, Rosenberg PS, Adami HO et al (2014) A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc 89(3):335–345. doi:10.1016/j.mayocp.2013.11.011
Irwin ML, McTiernan A, Bernstein L, Gilliland FD, Baumgartner R, Baumgartner K et al (2004) Physical activity levels among breast cancer survivors. Med Sci Sports Exerc 36(9):1484–1491
McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R et al (2003) Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 21(10):1961–1966. doi:10.1200/JCO.2003.07.057
Wayne SJ, Baumgartner K, Baumgartner RN, Bernstein L, Bowen DJ, Ballard-Barbash R (2006) Diet quality is directly associated with quality of life in breast cancer survivors. Breast Cancer Res Treat 96(3):227–232
Ernster VL, Barclay J, Kerlikowske K, Wilkie H, Ballard-Barbash R (2000) Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program. Arch Intern Med 160(7):953–958
Lohman T, Roche A, Martorell R (1988) Anthropometric standardization reference manual. Human Kinetics, Champaign
Kriska A (1997) Modifiable activity questionnaire. Med Sci Sports Exerc 29(6):73–78
Irwin ML, Smith AW, McTiernan A, Ballard-Barbash R, Cronin K, Gilliland FD et al (2008) Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol 26(24):3958–3964. doi:10.1200/jco.2007.15.9822
Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the women’s health initiative food frequency questionnaire. Ann Epidemiol 9(3):178–187
Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124(3):453–469
Guenther PM, Krebs-Smith SM, Reedy J, Britten P, Juan W, Lino M et al (2008) Healthy Eating Index-2005. United States Department of Agriculture, Center for Nutrition Policy and Promotion, Beltsville
Guenther PM, Reedy J, Krebs-Smith SM (2008) Development of the Healthy Eating Index-2005. J Am Diet Assoc 108(11):1896–1901. doi:10.1016/j.jada.2008.08.016
Guenther PM, Reedy J, Krebs-Smith SM, Reeve BB (2008) Evaluation of the Healthy Eating Index-2005. J Am Diet Assoc 108(11):1854–1864. doi:10.1016/j.jada.2008.08.011
Guenther PM, Reedy J, Krebs-Smith SM, Reeve BB, Basiotis PP (2007) Development and evaluation of the healthy eating index-2005: technical report: center for nutrition policy and promotion. U.S Department of Agriculture, Alexandria
U.S. Department of Health and Human Services and U.S. Department of Agriculture (2005) Dietary guidelines for Americans, 6th edn. U.S. Government Printing Office, Washington, DC
George SM, Irwin ML, Smith AW, Neuhouser ML, Reedy J, McTiernan A et al (2011) Postdiagnosis diet quality, the combination of diet quality and recreational physical activity, and prognosis after early-stage breast cancer. Cancer Causes Control 22(4):589–598. doi:10.1007/s10552-011-9732-9
Schakel SF, Buzzard IM, Gebhardt SE (1997) Procedures for estimating nutrient values for food composition databases. J Food Compos Anal 10:102–114
Schakel SF, Sievert YA, Buzzard IM (1988) Sources of data for developing and maintaining a nutrient database. J Am Diet Assoc 88(10):1268–1271
MyPyramid Equivalents Database, 2.0 for USDA Survey Foods, 2003–2004 [database on the Internet] (2008). Food Surveys Research Group. Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD. http://www.ars.usda.gov/ba/bhnrc/fsrg. Accessed 1 May 2014
Ledue TB, Weiner DL, Sipe JD, Poulin SE, Collins MF, Rifai N (1998) Analytical evaluation of particle-enhanced immunonephelometric assays for C-reactive protein, serum amyloid A and mannose-binding protein in human serum. Ann Clin Biochem 35(Pt 6):745–753
Irwin ML, Duggan C, Wang CY, Smith AW, McTiernan A, Baumgartner RN et al (2011) Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study. J Clin Oncol 29(1):47–53. doi:10.1200/JCO.2010.28.4752
Duggan C, Irwin ML, Xiao L, Henderson KD, Smith AW, Baumgartner RN et al (2011) Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol 29(1):32–39. doi:10.1200/JCO.2009.26.4473
Duggan C, Wang CY, Neuhouser ML, Xiao L, Smith AW, Reding KW et al (2013) Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer. Int J Cancer 132(5):1191–1200. doi:10.1002/ijc.27753
Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH et al (2009) Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 27(21):3437–3444. doi:10.1200/jco.2008.18.9068
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112(17):2735–2752. doi:10.1161/CIRCULATIONAHA.105.169404
Villaseñor A, Ballard-Barbash R, Baumgartner K, Baumgartner R, Bernstein L, McTiernan A, Neuhouser ML (2012) Prevalence and prognostic effect of sarcopenia in breast cancer survivors; the HEAL Study. Journal of Cancer Survivorship: Research and Practice 6:398–406
Kwan ML, John EM, Caan BJ, Lee VS, Bernstein L, Cheng I et al (2014) Obesity and mortality after breast cancer by race/ethnicity: the California Breast Cancer Survivorship Consortium. Am J Epidemiol 179(1):95–111. doi:10.1093/aje/kwt233
Tao MH, Shu XO, Ruan ZX, Gao YT, Zheng W (2006) Association of overweight with breast cancer survival. Am J Epidemiol 163(2):101–107. doi:10.1093/aje/kwj017
Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K et al (2008) General and abdominal adiposity and risk of death in Europe. N Engl J Med 359(20):2105–2120. doi:10.1056/NEJMoa0801891
Acknowledgments
We would like to thank Dr. Charles L. Wiggins, Dr. Anne McTiernan, Anita Ambs, HEAL study managers, Todd Gibson of Information Management Systems, and the HEAL study participants. This study was supported by the National Cancer Institute Grants N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010, and, in part, by the Applied Research Program of the National Cancer Institute.
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George, S.M., Bernstein, L., Smith, A.W. et al. Central adiposity after breast cancer diagnosis is related to mortality in the Health, Eating, Activity, and Lifestyle study. Breast Cancer Res Treat 146, 647–655 (2014). https://doi.org/10.1007/s10549-014-3048-x
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DOI: https://doi.org/10.1007/s10549-014-3048-x