Abstract
Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Furthermore, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)–positive breast cancer.
This was a case–cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study. We measured insulin, c-peptide, IGF-1, insulin-like growth factor binding protein-3, and biomarkers of inflammatory and sex-steroid hormone pathways. Poisson regression with a robust variance estimator was used to estimate risk ratios (RR) and 95% confidence intervals (95% CI) for ER-positive breast cancer per doubling plasma concentration and for quartiles, without and with adjustment for other, potentially confounding biomarkers.
ER-positive breast cancer risk was not associated with doubling of insulin (RR = 0.97, 95% CI, 0.82–1.14) or c-peptide (RR = 1.01, 95% CI, 0.80–1.26). Risk seemed to decrease with doubling IGF-1 (RR = 0.80, 95% CI, 0.62–1.03) and insulin-like growth factor binding protein-3 (RR = 0.62, 95% CI, 0.41–0.90). RRs were not meaningfully different when exposures were modeled as quartiles. RRs were less than unity but imprecise after adjustment for inflammatory and sex-steroid hormone biomarkers.
Circulating insulin, c-peptide, and IGF-1 were not positively associated with risk of ER-positive breast cancer in this case–cohort analysis of postmenopausal women.
Associations between insulin and c-peptide and risk of ER-positive breast cancer in postmenopausal women are likely to be weak.