Insulin and insulin-like growth factor and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Background: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Further, 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.

Methods: 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 (IGFBP-3), and biomarkers of inflammatory and sex-steroid hormone pathways. Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (95% CIs) for ER-positive breast cancer per doubling plasma concentration and for quartiles, without and with adjustment for other, potentially confounding biomarkers.

Results: 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 appeared to decrease with doubling IGF-1 (RR = 0.80, 95% CI: 0.62, 1.03) and IGFBP-3 (RR = 0.62, 95% CI: 0.41, 0.90). RRs were not meaningfully different when exposures were modelled as quartiles. RRs were less than unity but imprecise after adjustment for inflammatory and sex-steroid hormone biomarkers.

Conclusions: 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.

Impact: Associations between insulin and c-peptide and risk of ER-positive breast cancer in postmenopausal women are likely to be weak.