Plasma C-peptide, Mammographic Density Parameters, Mammographic Texture Feature, and Risk of Breast Cancer

Abstract

Abstract Background High levels of insulin may increase the risk of breast cancer (BC). We studied the association between C-peptide levels as a marker of high-level endogenous insulin, mammographic density (MD) parameters, and BC risk. We also examined the association between C-peptide and BC risk varies by MD status. Methods: We conducted a nested case-control study (n=1260 cases; n=2221 controls) in the Nurses’ Health Study (NHS) and NHS2. We assessed MD parameters and V (a measure of grayscale variation). MD parameters were square root-transformed. Linear and logistic regression models were used to analyze the associations between C-peptide and MD parameters among controls, and C-peptide with breast cancer, respectively. Multivariable models were adjusted for matching factors and established risk factors for BC. Results: In multivariable models including BMI, C-peptide was significantly inversely associated with percent MD and positively associated with non-dense area. However, no associations were detected with dense area and V measure. C-peptide was associated with an increased risk of invasive BC (top vs. bottom quartile, odds ratio = 1.40, 95% confidence interval :1.08 to 1.81). The association was stronger for ER-negative disease (adjusted OR=1.82, 95% CI: 1.13 to 2.94), though heterogeneity by ER status was not significant. There was no significant heterogeneity by menopausal status. There was no evidence of multiplicative interaction between C-peptide, and MD parameters and risk of BC (All p-interactions>0.11). Conclusion Our results suggest a positive association between C-peptide and BC risk. Furthermore, MD parameters do not seem to modify the association between C-peptide and BC risk.