Abstract CT093: Caloric restriction improves radiation-induced oncomiR induction in a clinical trial of breast cancer patients

Abstract

Abstract Background: miRNA-21, a well-known onco-miR, has been found to be up-regulated in over 18 major cancer types and is linked to radiation and chemotherapy resistance. It has been widely reported that radiation induces mir-21 expression levels in several different types of cancer and is also associated with cancer recurrence. Our laboratory has demonstrated increased radiation sensitivity in a miR-21 knockout mouse and has shown that these mice are 10-fold more sensitive to radiation than are their wild type (WT) counterparts. We have also shown that decreasing mir-21 levels have a beneficial effect in breast cancer mouse models. Evidence shows that miR-21 is controlled by metabolism. These findings have spurred growing interest in the potential role of caloric restriction (CR), i.e. a diet modification involving a 20-30% reduction in the total caloric intake, as a treatment modality for age-related diseases such as cancer. We began the first-in-human clinical trial using CR during radiation to determine if miR-21 could be decreased. Methods: 36 patients were accrued from 2013-2016 and enrolled on an IRB approved study. Patients with Stage 0 or 1 breast cancer had nutritional counseling to decrease their caloric intake by 25% compared with their baseline. Patients underwent caloric restriction for 10 weeks: 2 weeks of CR alone, 6 weeks of diet and radiation to a dose of 60Gy and 2 weeks of CR alone after radiation. Patients were evaluated before and after the 10 weeks of diet and radiation for biometric properties, quality of life and serum measures. Serum measures were compared to samples of patients who had radiation alone without CR. Results: Compared with radiation controls, mir-21 levels decreased by almost 100-fold. Overall, 33/36 (91.7%) of patients were able to adhere to the 25% reduction in calories and lost an average of 9.1pounds with a 3 pound average weight gain seen in historic controls. Over ten weeks, their serum profiles improved with CR regimen: decreases in insulin, IGF-1, triglycerides, leptin and an increase in adiponectin. Since we had hypothesized that CR would protect normal tissue, acute skin toxicity from radiation was documented in this pilot study. We found that CR decreases the moist desquamation rate significantly compared with historic controls. Quality-of-life measures with the fatigue index and FACT-B also improved. Conclusions: Further clinical trials are warranted to evaluate of the ability of caloric restriction to 1) augment radiation and 2) decrease radiation resistance by decreasing the reflexive increase of miR-21. Citation Format: Nicole L. Simone, Adam Berger, Pramila R. Anne, Kevin Ko, Tiziana DeAngelis, Brittany Simone, Sunny Han, Ajay Palagani, Andrew Newberg, Daniel Monti. Caloric restriction improves radiation-induced oncomiR induction in a clinical trial of breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT093. doi:10.1158/1538-7445.AM2017-CT093