Abstract PO-096: Caloric restriction may decrease health disparity in AA breast cancer patients due to significant downregulation of the IGF-1R pathway in a window-of-opportunity clinical trial
Authors: Okere Samantha , Shastri Anuradha A. , Hines Kamryn , Anne Pramila , Murphy Rita , DeAngelis Tiziana , Berger Adam , Willis Alliric , Lazar Melissa , Mitchell Edith , Simone Nicole 
Published: January 2022

Introduction: Health disparities in breast cancer outcomes exist for African American (AA) women who are noted to present with more aggressive cancer with worse survival. Although the underlying reason for this disparity is not apparent, it is likely multifactorial. Interestingly, type 1 insulin-like growth factor receptor (IGF-1R) expression, which plays a critical role in cell growth, survival, and migration, is higher in normal breast tissue in AA women as compared to Caucasian women. Although this has been well established, interventional studies to modulate this pathway have not been performed. We sought to determine if a dietary intervention of caloric restriction could play a role in modulating the IGF-1R pathway to help address the disparities seen in AA breast cancer patients. Methods: On an IRB approved clinical trial, patients were enrolled in a window-of-opportunity clinical trial to assess the effect of caloric restriction, or a 25% reduction of calories from the patients' baseline, on biomarkers in the tumor and blood. Patients recorded their baseline caloric intake for 3-5 days and were then instructed on a target calorie intake for the remainder of the diet. The patients remained on the dietary intervention for 2-12 weeks. Participants had anthropometric evaluation, blood draws to evaluate serum cytokines, tissue collection, and quality of life surveys collected at baseline and completion of diet which was the morning of surgery. Results: We enrolled 19 breast cancer patients between the years 2016 and 2018. The average age of the patients at the time of enrollment was 58 years old with 47% AA and 53% Caucasian. The patients were on the trial for an average of 19 days. Patients lost an average of 4.91 lbs during the trial, with AA patients losing an average of 5.18 lbs and Caucasians losing an average of 4.68 lbs. To determine the importance of IGF-1R in the disparities seen in AA women, we looked at two hundred cytokines from serum samples in patients who underwent caloric restriction. Analysis of the cytokine array data showed that nine cytokines involved in regulating or modulation by the IGF-1R pathway were significantly (p&lt;0.05) downregulated in AA women post-diet. Compared to Caucasian women, AA women showed a significant decrease in IL-12p40 (~51%), VCAM1 (16.8%), IL-2 (28.72%), IL-2Rb (40.81%), CCL28 (36%), ERBB3 (26.6%), PAI-1 (9.4%), Axl (36%) and PDGF-AB (12%). Conclusion: These results demonstrate that caloric restriction significantly downregulated members of the IGF-1R pathway in the AA community. Since this pathway is notably dysregulated in AA patients, an integrated approach, one incorporating dietary changes to alter key pro-survival pathways, should be further investigated to narrow the disparity in breast cancer outcomes in AA patients.

Citation Format: Samantha Okere, Anuradha A. Shastri, Kamryn Hines, Pramila Anne, Rita Murphy, Tiziana DeAngelis, Adam Berger, Alliric Willis, Melissa Lazar, Edith Mitchell, Nicole Simone. Caloric restriction may decrease health disparity in AA breast cancer patients due to significant downregulation of the IGF-1R pathway in a window-of-opportunity clinical trial [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-096.