Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease

Chelsea Catsburg, Marc J. Gunter, Chu Chen, Michele L. Cote, Geoffrey C. Kabat, Rami Nassir, Lesley Tinker, Jean Wactawski-Wende, David L. Page, Thomas E. Rohan

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 with in 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.

Original languageEnglish (US)
Pages (from-to)3248-3258
Number of pages11
JournalCancer Research
Volume74
Issue number12
DOIs
StatePublished - Jun 15 2014

Fingerprint

Breast Diseases
Estrogens
Insulin
Adiponectin
C-Reactive Protein
Breast Neoplasms
Estradiol
Fasting
Logistic Models
Serum
Hormones
Inflammation
Social Adjustment
Hyperinsulinism
Women's Health
Progestins
Adipose Tissue
Case-Control Studies
Clinical Trials
Confidence Intervals

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease. / Catsburg, Chelsea; Gunter, Marc J.; Chen, Chu; Cote, Michele L.; Kabat, Geoffrey C.; Nassir, Rami; Tinker, Lesley; Wactawski-Wende, Jean; Page, David L.; Rohan, Thomas E.

In: Cancer Research, Vol. 74, No. 12, 15.06.2014, p. 3248-3258.

Research output: Contribution to journalArticle

Catsburg, C, Gunter, MJ, Chen, C, Cote, ML, Kabat, GC, Nassir, R, Tinker, L, Wactawski-Wende, J, Page, DL & Rohan, TE 2014, 'Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease', Cancer Research, vol. 74, no. 12, pp. 3248-3258. https://doi.org/10.1158/0008-5472.CAN-13-3514
Catsburg C, Gunter MJ, Chen C, Cote ML, Kabat GC, Nassir R et al. Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease. Cancer Research. 2014 Jun 15;74(12):3248-3258. https://doi.org/10.1158/0008-5472.CAN-13-3514
Catsburg, Chelsea ; Gunter, Marc J. ; Chen, Chu ; Cote, Michele L. ; Kabat, Geoffrey C. ; Nassir, Rami ; Tinker, Lesley ; Wactawski-Wende, Jean ; Page, David L. ; Rohan, Thomas E. / Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease. In: Cancer Research. 2014 ; Vol. 74, No. 12. pp. 3248-3258.
@article{3eadb167370b4e2a805f19a90f5c15c1,
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 with in 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.",
author = "Chelsea Catsburg and Gunter, {Marc J.} and Chu Chen and Cote, {Michele L.} and Kabat, {Geoffrey C.} and Rami Nassir and Lesley Tinker and Jean Wactawski-Wende and Page, {David L.} and Rohan, {Thomas E.}",
year = "2014",
month = "6",
day = "15",
doi = "10.1158/0008-5472.CAN-13-3514",
language = "English (US)",
volume = "74",
pages = "3248--3258",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Insulin, estrogen, inflammatory markers, and risk of benign proliferative breast disease

AU - Catsburg, Chelsea

AU - Gunter, Marc J.

AU - Chen, Chu

AU - Cote, Michele L.

AU - Kabat, Geoffrey C.

AU - Nassir, Rami

AU - Tinker, Lesley

AU - Wactawski-Wende, Jean

AU - Page, David L.

AU - Rohan, Thomas E.

PY - 2014/6/15

Y1 - 2014/6/15

N2 - 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 with in 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.

AB - 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 with in 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.

UR - http://www.scopus.com/inward/record.url?scp=84903449144&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903449144&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-13-3514

DO - 10.1158/0008-5472.CAN-13-3514

M3 - Article

C2 - 24755474

AN - SCOPUS:84903449144

VL - 74

SP - 3248

EP - 3258

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 12

ER -