Insulinemic potential of diet and risk of total and subtypes of breast cancer among US females

Abstract

Background: Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diets with higher insulinemic potential increase the risk of invasive breast cancer. Objectives: We aimed to prospectively evaluate the association between a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer. Methods: We prospectively followed 76,686 women from the Nurses’ Health Study (NHS; 1984–2016) and 93,287 women from the Nurses’ Health Study II (NHSII; 1991–2017). Diet was assessed by food-frequency questionnaires every 4 y. The insulinemic potential of diet was evaluated using the previously established EDIH based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential of the diet. Covariates included reproductive, hormonal, and anthropometric factors (height and BMI at age 18 y); race; socioeconomic status; total alcohol intake; total caloric intake; and physical activity. Results: During 4,216,106 person-years of follow-up, we documented 10,602 breast cancer cases (6689 NHS, 3913 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIH quintile (Q) were at higher breast cancer risk (HRQ5 vs. Q1 = 1.15; 95% CI: 1.07, 1.24; P-trend < 0.01). Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association between EDIH and breast cancer was observed for ER-negative tumors (HRQ5 vs. Q1 = 1.21; 95% CI: 1.00, 1.46; P-trend = 0.02). Among tumor molecular subtypes, the strongest associations were observed for human epidermal growth factor receptor 2 (HER2)–enriched tumors (HRQ5 vs. Q1 = 1.62; 95% CI: 1.01, 2.61; P-trend = 0.02). Conclusions: A dietary pattern contributing to hyperinsulinemia and insulin resistance was associated with greater breast cancer risk, especially ER-negative and HER2-enriched tumors. Our findings suggest that dietary modifications to reduce insulinemic potential may reduce the risk of breast cancer.