Abstract

Abstract Background: Hyperinsulinemia may promote the growth and metastasis of breast cancers by activating the insulin/insulin-like growth factor 1 signaling pathways. Whether the insulinemic potential of the diet contributes to breast cancer prognosis has not been examined previously. Here, we focused on a food-based empirical dietary index for hyperinsulinemia (EDIH), an index previously designed as most predictive of fasting plasma C-peptide. We aimed to investigate whether EDIH (at different time settings) is associated with overall and breast cancer-specific mortality. Methods: For 9,640 women with stage I-III breast cancer from the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII), we calculated the cumulative average EDIH, using repeated measures of post-diagnostic diet from food frequency questionnaires (FFQ). We also considered the pre-diagnostic EDIH score (using the last FFQ reported before diagnosis), the first postdiagnostic EDIH score, as well as a simple updated EDIH score. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. Deaths were ascertained by report from family members or by searching the National Death Index. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Results: Participants were followed up for a median of 12 years after breast cancer diagnosis. We documented 1,120 deaths due to breast cancer and 2,762 all-cause deaths. Women with higher post-diagnostic EDIH had a 40% higher risk of all-cause mortality (HR for quintile 5 vs. quintile 1 [HRQ5vs.Q1], 1.40; 95% CI, 1.22, 1.61; P-trend<0.0001). EDIH was also associated with a 19% increased risk of breast cancer mortality, although the confidence interval included the null (HRQ5vs.Q1, 1.19; 95% CI, 0.95, 1.48; P-trend=0.17). Findings for overall mortality were similar for EDIH measured at other timings/settings: last pre-diagnosis dietary assessment (HRQ5vs.Q1,1.21; 95% CI, 1.06, 1.39; P-trend<0.0001) and first post-diagnosis dietary assessment (HRQ5vs.Q1,1.23; 95% CI, 1.08, 1.40; P-trend<0.0001). Conclusions: In this large prospective study of breast cancer survivors, higher hyperinsulinemic dietary scores (reflecting higher dietary insulinemic potential) were associated with worse survival outcomes following diagnosis. Thus, dietary recommendations emphasizing the importance of avoiding high insulinemic dietary patterns (i.e., processed meat and red meat) and prioritizing low insulinemic dietary patterns (i.e., coffee, whole fruit and green-leafy vegetables) as components of a healthy diet may improve overall survival. Citation Format: Andrea Romanos-Nanclares, Tengteng Wang, Bernard A. Rosner, Michelle D. Holmes, Wendy Y. Chen, Walter C. Willett, Rulla M. Tamimi, A. Heather Eliassen. Dietary insulinemic potential and survival after breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2218.

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