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Breast Cancer Risk in Metabolically Healthy but Overweight Postmenopausal Women

Marc J. Gunter, Xianhong Xie, Xiaonan Xue, Geoffrey C. Kabat, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Gloria Y.F. Ho, Judith Wylie-Rosett, Theresa Greco, Herbert Yu, Jeannette Beasley and Howard D. Strickler
Marc J. Gunter
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
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  • For correspondence: m.gunter@imperial.ac.uk
Xianhong Xie
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Xiaonan Xue
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Geoffrey C. Kabat
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Thomas E. Rohan
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Sylvia Wassertheil-Smoller
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Gloria Y.F. Ho
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Judith Wylie-Rosett
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Theresa Greco
Stanford University, Stanford, California.
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Herbert Yu
University of Hawaii Cancer Center, Honolulu, Hawaii.
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Jeannette Beasley
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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Howard D. Strickler
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, New York.
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DOI: 10.1158/0008-5472.CAN-14-2317 Published January 2015
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Abstract

Adiposity is an established risk factor for postmenopausal breast cancer. Recent data suggest that high insulin levels in overweight women may play a major role in this relationship, due to insulin's mitogenic/antiapoptotic activity. However, whether overweight women who are metabolically healthy (i.e., normal insulin sensitivity) have elevated risk of breast cancer is unknown. We investigated whether overweight women with normal insulin sensitivity [i.e., homeostasis model assessment of insulin resistance (HOMA-IR) index, or fasting insulin level, within the lowest quartile (q1)] have increased breast cancer risk. Subjects were incident breast cancer cases (N = 497) and a subcohort (N = 2,830) of Women's Health Initiative (WHI) participants with available fasting insulin and glucose levels. In multivariate Cox models, metabolically healthy overweight women, defined using HOMA-IR, were not at elevated risk of breast cancer compared with metabolically healthy normal weight women [HRHOMA-IR, 0.96; 95% confidence interval (CI), 0.64–1.42]. In contrast, the risk among women with high (q3-4) HOMA-IRs was elevated whether they were overweight (HRHOMA-IR, 1.76; 95% CI, 1.19-2.60) or normal weight (HRHOMA-IR, 1.80; 95% CI, 0.88–3.70). Similarly, using fasting insulin to define metabolic health, metabolically unhealthy women (insulin q3-4) were at higher risk of breast cancer regardless of whether they were normal weight (HRinsulin, 2.06; 95% CI, 1.01–4.22) or overweight (HRinsulin, 2.01; 95% CI, 1.35–2.99), whereas metabolically healthy overweight women did not have significantly increased risk of breast cancer (HRinsulin, 0.96; 95% CI, 0.64–1.42) relative to metabolically healthy normal weight women. Metabolic health (e.g., HOMA-IR or fasting insulin) may be more biologically relevant and more useful for breast cancer risk stratification than adiposity per se. Cancer Res; 75(2); 270–4. ©2014 AACR.

  • Received August 8, 2014.
  • Revision received October 27, 2014.
  • Accepted November 3, 2014.
  • ©2014 American Association for Cancer Research.
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Cancer Research: 75 (2)
January 2015
Volume 75, Issue 2
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Breast Cancer Risk in Metabolically Healthy but Overweight Postmenopausal Women
Marc J. Gunter, Xianhong Xie, Xiaonan Xue, Geoffrey C. Kabat, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Gloria Y.F. Ho, Judith Wylie-Rosett, Theresa Greco, Herbert Yu, Jeannette Beasley and Howard D. Strickler
Cancer Res January 15 2015 (75) (2) 270-274; DOI: 10.1158/0008-5472.CAN-14-2317

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Breast Cancer Risk in Metabolically Healthy but Overweight Postmenopausal Women
Marc J. Gunter, Xianhong Xie, Xiaonan Xue, Geoffrey C. Kabat, Thomas E. Rohan, Sylvia Wassertheil-Smoller, Gloria Y.F. Ho, Judith Wylie-Rosett, Theresa Greco, Herbert Yu, Jeannette Beasley and Howard D. Strickler
Cancer Res January 15 2015 (75) (2) 270-274; DOI: 10.1158/0008-5472.CAN-14-2317
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