Abstract

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 diet with higher insulinemic potential is associated with invasive breast cancer risk.Objectives: We prospectively evaluated the association between adherence to a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer.Methods: We prospectively followed 76,595 women from the Nurses’ Health Study (NHS, 1984-2016) and 93,295 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using the EDIH that was pre-defined based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential, while lower scores indicate lower insulinemic potential.Results: During 4,215,162 person-years of follow-up, we documented 10,595 breast cancer cases (6,639 NHS; 3,914 NHSII). Being in the highest, compared with the lowest, EDIH quintile was associated with higher breast cancer risk (HRQ5vsQ1 1.18; 95% CI 1.10, 1.27; P-trend<0.01). The association was suggestively strongest among women with current BMI<25 kg/m2 (HRQ5vsQ1 1.20; 95% CI 1.08, 1.34; P-trend<0.01; P-interaction=0.06) compared to overweight/obese women. Although heterogeneity by estrogen receptor (ER) status was non-significant (P=0.17), the strongest association between EDIH and breast cancer was observed with ER-negative tumors (HRQ5vsQ1 1.26; 95% CI 1.04, 1.51; P-trend<0.01). Among tumor molecular subtypes, the strongest associations were observed with HER2-enriched tumors (HRQ5vsQ1 1.75; 95% CI 1.08, 2.82; P-trend=0.01).Conclusions: A dietary pattern contributing to hyperinsulinemia was associated with greater breast cancer risk in women from the NHS/NHSII. In particular, a more hyperinsulinemic diet was associated with higher risk of breast cancer among lean women when compared to overweight or obese women. Moreover, the hyperinsulinemic diet showed a stronger positive association with ER-negative breast tumors, independent of adiposity. Our findings suggest that dietary interventions to reduce insulinemic potential may have a role in breast cancer prevention. Citation Format: Andrea Romanos-Nanclares, Walter C. Willett, Bernard A. Rosner, Rulla M. Tamimi, Fred K. Tabung, Michelle D. Holmes, Wendy Y Chen, A. Heather Eliassen. Insulinemic potential of diet and risk of total and subtypes of breast cancer among US women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-09-06.

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