title: Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease.
abstract: Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up, and they were matched to 1,321 controls. Levels of insulin, estradiol, C-reactive protein (CRP), and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate ORs for the association of each factor with BPBD risk. Among nonusers of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile = 1.80; 95% confidence interval, CI, 1.16-2.79; Ptrend = 0.003) as were levels of estradiol (OR for highest vs. lowest tertile = 1.89; 95% CI, 1.26-2.83; Ptrend = 0.02) and CRP (OR for highest vs. lowest quartile = 2.46; 95% CI, 1.59-3.80; Ptrend < 0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile = 0.47; 95% CI, 0.31-0.71; Ptrend < 0.001). These associations persisted after mutual adjustment, but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP, and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin, and inflammation pathways are associated with the early stages of breast cancer development.
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Catsburg
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Cote
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Kabat
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Rami
authors.initials: R
authors.lastname: Nassir
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Lesley
authors.initials: L
authors.lastname: Tinker
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: David L
authors.initials: DL
authors.lastname: Page
authors.affiliation: Authors' Affiliations: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx; Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, New York; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan; Department of Public Health Sciences, University of California - Davis, Davis, California; Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom Thomas.Rohan@einstein.yu.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007328:Insulin / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause; D011230:Precancerous Conditions / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D052242:Adiponectin; D004967:Estrogens; D018836:Inflammation Mediators; D007328:Insulin; D004958:Estradiol; D002097:C-Reactive Protein