Plasma C-peptide, mammographic breast density, and risk of invasive breast cancer.

Abstract

BACKGROUND:

Insulin may promote breast cancer directly by stimulating the insulin receptor or indirectly by increasing the plasma concentration of active sex hormones. The association between insulin and breast density, a strong breast cancer risk factor, has not been thoroughly studied. We measured associations between c-peptide (a molar marker of insulin secretion), breast cancer risk, and breast density measurements in case-control studies nested within the Nurses' Health Study and Nurses' Health Study II cohorts.

METHODS:

Breast cancer associations were estimated with multivariate logistic regression models and then pooled across cohorts (total n = 1,084 cases and 1,785 controls). Mammographic density associations (percent dense area, dense area, and nondense area) were estimated as the difference in least-square means of the density parameters between quartiles of c-peptide concentration in all breast cancer controls with available screening mammography films (n = 1,469).

RESULTS:

After adjustment for adiposity, c-peptide was not associated with any measure of breast density. However, c-peptide was associated with an approximately 50% increased risk of invasive breast cancer [top vs. bottom quartile, adjusted OR = 1.5, 95% confidence interval (CI), 1.1-2.0] that was robust to adjustment for plasma-free estradiol and sex hormone-binding globulin. The association was stronger for ER-negative disease (adjusted OR = 2.0; 95% CI, 1.2-3.6).

CONCLUSIONS:

Our data suggest a positive association between hyperinsulinemia and breast cancer risk that occurs through nonestrogenic mechanisms, and that is not mediated by breast density.

IMPACT:

Primary prevention of breast cancer in women with hyperinsulinemia may be possible by targeting insulin signaling pathways.

• Authors: Thomas P Ahern, Susan E Hankinson, Walter C Willett, Michael N Pollak, A Heather Eliassen, Rulla M Tamimi
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 22 Issue 10 Pg. 1786-96 (Oct 2013) ISSN: 1538-7755 [Electronic] United States
• PMID: 24097198 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• C-Peptide

Topics

• Breast Density
• Breast Neoplasms (blood, diagnostic imaging, pathology)
• C-Peptide (metabolism)
• Cohort Studies
• Female
• Humans
• Logistic Models
• Mammary Glands, Human (abnormalities)
• Middle Aged
• Radiography
• Risk Factors