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


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.


CONCLUSIONS
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.
Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., MD-B306, Seattle, WA 98104, USA. cduggan@fhcrc.org
Catherine
C
Duggan
Melinda L
ML
Irwin
Liren
L
Xiao
Katherine D
KD
Henderson
Ashley Wilder
AW
Smith
Richard N
RN
Baumgartner
Kathy B
KB
Baumgartner
Leslie
L
Bernstein
Rachel
R
Ballard-Barbash
Anne
A
McTiernan
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000401:mortality; D011446:Prospective Studies; D012307:Risk Factors
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin