Associations of insulin resistance and adiponectin with mortality in women with breast cancer

Abstract

Purpose: Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality.

Patients and methods: We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models.

Results: Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer-specific or all-cause mortality.

Conclusion: Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors.

Fig 1.

Participant recruitment and timing of data collection. UNM, University of New Mexico; FHCRC, Fred Hutchinson Cancer Research Center; USC, University of Southern California. (*) Survey completed following diagnosis: UNM (mean, 5 months; range, 1 to 9 months), FHCRC (mean, 8 months; range, 3 to 23 months), and USC (mean, 6 months; range, 2 to 17 months). (†) For USC, weight and height 5 years prior to diagnosis were self-reported on baseline survey, ([doubledagger]) Assessment completed post baseline: UNM (mean, 23 months; range 17 to 32 months), FHCRC (mean, 24 month; range, 12 to 29 months), and USC (mean, 27 months; range, 23 to 45 months).