Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women's Health Initiative

Cancer. 2020 Aug 15;126(16):3638-3647. doi: 10.1002/cncr.33002. Epub 2020 Jun 12.


Background: Insulin resistance is associated with higher all-cause and cancer-specific mortality in postmenopausal women. However, to the authors' knowledge, information regarding insulin resistance and breast cancer mortality risk is limited. Therefore, the authors examined associations between insulin resistance and breast cancer incidence and mortality in a subsample of Women's Health Initiative participants.

Methods: A total of 22,837 postmenopausal women with fasting baseline glucose and insulin levels were followed for incident breast cancer and breast cancer mortality. Breast cancers were verified by medical record review and serial National Death Index linkage-enhanced mortality findings. Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR). Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) with 95% confidence intervals (95% CIs) for quartile comparisons. Outcomes included breast cancer incidence, deaths from breast cancer, and deaths after breast cancer (breast cancer followed by death from any cause).

Results: During a median of 19.8 years of follow-up of 1328 breast cancer cases, there were 512 deaths reported, 151 of which were from breast cancer. Breast cancer incidence was higher in women in the highest HOMA-IR quartile (HR, 1.34; 95% CI, 1.12-1.61 [P for trend = .003]). Although HOMA-IR was not found to be associated with risk of death from breast cancer (HR, 1.04; 95% CI, 0.60-1.79), women in the highest versus those in the lowest HOMA-IR quartile were at a higher risk of death after breast cancer (HR, 1.78; 95% CI, 1.32-2.39 [P for trend <.001]).

Conclusions: Higher levels of insulin resistance in postmenopausal women are associated with higher breast cancer incidence and higher all-cause mortality after breast cancer.

Keywords: Women's Health Initiative; breast cancer; breast cancer mortality; homeostatic model assessment of insulin resistance (HOMA-IR); insulin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Blood Glucose
  • Body Mass Index
  • Breast / diagnostic imaging*
  • Breast / pathology
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Data Management
  • Fasting
  • Female
  • Humans
  • Insulin Resistance / genetics*
  • Mammography
  • Middle Aged
  • Postmenopause / genetics
  • Proportional Hazards Models
  • Risk Factors
  • Women's Health*


  • Blood Glucose