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

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.