Low Glycemic Index Diet, Exercise and Vitamin D to Reduce Breast Cancer Recurrence: Rationale for the Design of a Clinical Trial
Authors: Augustin Livia Silvia , Libra Massimo , Crispo Anna , Grimaldi Maria , Candido Saverio , Falzone Luca , De Laurentiis Michelino , Garland Cedric F. , Jenkins David J.A. , Kendall Cyril W.C. , Ciliberto Gennaro , Montella Maurizio 
Published: November 2023

BackgroundBreast cancer (BC) survival rates in Europe reach about 70% suggesting a large residual risk. Women with BC may suffer from other chronic conditions (diabetes) which increase the risk of recurrence and reduce survival. Mechanisms of BC include hyperglycemia, hyperinsulinemia, high estrogen levels, insulin‐like growth factors (IGF), inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods have low glycemic and insulinemic potentials and have been associated with lower BC risk. Moderate physical activity post‐diagnosis reduces BC recurrence and mortality which is partly explained by reduced insulin and estrogen levels. Vitamin D alters genes implicated in cell differentiation/apoptosis and high serum vitamin D levels have shown improved BC survival. Dietary interventions have been associated with molecular changes (microRNA) which can alter cellular signaling (IGF‐1). To our knowledge no trial has evaluated the combined effect of a lifestyle program with focus on low GI, additional physical activity and supplemental vitamin D on BC recurrence in the context of a Mediterranean lifestyle setting.Hypothesis and ObjectivesOur hypothesis is that the program of low GI diet, vitamin D and exercise will significantly reduce BC recurrence in women with BC by 12%. Primary objective: to test the effectiveness of the program in reducing BC recurrence. Secondary objectives: to test the potential effects of the program on cardiometabolic profiles, on adjuvant therapy side effects and quality of life. Tertiary objectives: to identify distinct plasma miRNA expression patterns associated with BC recurrence.Setting and MethodsWomen with BC (n=506) who had undergone surgery for primary histologically confirmed BC within the previous 12 months (stage II and III without metastasis) in cancer centres in Italy, will be randomized to follow for 3 years either the high intensity arm (low GI + exercise + vitamin D to reach serum 80ng/mL) or the lower intensity arm (general advice on a healthy diet and exercise + vitamin D to avoid insufficiency). Both interventions are on a background of Mediterranean diet. Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 3‐day food records will be collected.ResultsThis presentation will discuss the rationale and methodology of our study and potential issues.ConclusionsGiven the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients.Support or Funding InformationItalian Ministry of Health, Abiogen Pharma Spa, Barilla Spa