Background & Aims: Breast cancer recurrence risk is strongly influenced by metabolic and hormonal factors linked to adiposity and diet. The DIet ANd Androgens-5 (DIANA-5) randomized controlled trial was primarily designed to test whether adherence to a Mediterranean/macrobiotic diet, combined with moderate physical activity, could reduce the risk of breast cancer recurrence. In the present secondary analysis of the DIANA-5 trial, we investigated associations between dietary intake, anthropometric, metabolic and hormonal profile testing the hypothesis that improvement in metabolic and hormonal parameters after one year of intervention are mediated by increased consumption of recommended foods ("recommended food score") and changes of body composition measures. Methods: A total of 1542 women with early-stage breast cancer and presence of one or more endocrine/ metabolic risk factors were randomized to receive either standard healthy lifestyle recommendations (n = 773) or intensive support including dietary counseling, cooking classes, and moderate physical activity reinforcement (n = 769). Anthropometric (BMI, waist circumference [WC], fat mass/fat-free mass ratio [FM/FFM]), metabolic (glycemia, insulin, HOMA index, total cholesterol, triglycerides, metabolic syndrome), and hormonal (testosterone) endpoints were assessed at baseline and after 12 months. Potential mediation effects of "recommended food score" and WC or FM/FFM on metabolic and hormonal changes were tested by using SPSS version 23 and the PROCESS macro v.4.0 for SPSS. Results: 604 and 551 women were available for mediation analyses in intervention and control groups, respectively. The dietary intervention improved all anthropometric, metabolic and hormonal measures. "Recommended food score" together with WC mediated 73 % of the effect of the intervention on glycemia, 67 % on insulin, 70 % on HOMA index, 96 % on total cholesterol, and 86 % on metabolic syndrome. With "recommended food score" and FM/FFM as mediators, proportions mediated were 86 % for glycemia, 73 % for insulin, 78 % for HOMA index, 126 % for total cholesterol, and 66 % for metabolic syndrome. Mediation effects of WC and FM/FFM on triglyceride changes were much weaker (38 % and 37 %, respectively). For all outcomes and all mediators, at least one path had a p-value <0.05. Conclusions: Most benefits of the DIANA-5 lifestyle intervention were mediated by dietary adherence and reductions in WC and FM/FFM. The proportion of effects mediated on metabolic syndrome, glucose and glycemic tolerance is high enough to suggest that these are the main effectors. The results on triglyceride blood levels suggest that further mechanism, possibly physical activity and energy intake should be investigated. Clinical Trial Registry number: NCT05019989. Available at: https://clinicaltrials.gov/ search?cond=NCT05019989. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Diet, body composition and metabolic and hormonal profile in women at high risk of breast cancer recurrence: A secondary mediation analysis of the DIANA-5 trial
Villarini A.Membro del Collaboration Group
2026
Abstract
Background & Aims: Breast cancer recurrence risk is strongly influenced by metabolic and hormonal factors linked to adiposity and diet. The DIet ANd Androgens-5 (DIANA-5) randomized controlled trial was primarily designed to test whether adherence to a Mediterranean/macrobiotic diet, combined with moderate physical activity, could reduce the risk of breast cancer recurrence. In the present secondary analysis of the DIANA-5 trial, we investigated associations between dietary intake, anthropometric, metabolic and hormonal profile testing the hypothesis that improvement in metabolic and hormonal parameters after one year of intervention are mediated by increased consumption of recommended foods ("recommended food score") and changes of body composition measures. Methods: A total of 1542 women with early-stage breast cancer and presence of one or more endocrine/ metabolic risk factors were randomized to receive either standard healthy lifestyle recommendations (n = 773) or intensive support including dietary counseling, cooking classes, and moderate physical activity reinforcement (n = 769). Anthropometric (BMI, waist circumference [WC], fat mass/fat-free mass ratio [FM/FFM]), metabolic (glycemia, insulin, HOMA index, total cholesterol, triglycerides, metabolic syndrome), and hormonal (testosterone) endpoints were assessed at baseline and after 12 months. Potential mediation effects of "recommended food score" and WC or FM/FFM on metabolic and hormonal changes were tested by using SPSS version 23 and the PROCESS macro v.4.0 for SPSS. Results: 604 and 551 women were available for mediation analyses in intervention and control groups, respectively. The dietary intervention improved all anthropometric, metabolic and hormonal measures. "Recommended food score" together with WC mediated 73 % of the effect of the intervention on glycemia, 67 % on insulin, 70 % on HOMA index, 96 % on total cholesterol, and 86 % on metabolic syndrome. With "recommended food score" and FM/FFM as mediators, proportions mediated were 86 % for glycemia, 73 % for insulin, 78 % for HOMA index, 126 % for total cholesterol, and 66 % for metabolic syndrome. Mediation effects of WC and FM/FFM on triglyceride changes were much weaker (38 % and 37 %, respectively). For all outcomes and all mediators, at least one path had a p-value <0.05. Conclusions: Most benefits of the DIANA-5 lifestyle intervention were mediated by dietary adherence and reductions in WC and FM/FFM. The proportion of effects mediated on metabolic syndrome, glucose and glycemic tolerance is high enough to suggest that these are the main effectors. The results on triglyceride blood levels suggest that further mechanism, possibly physical activity and energy intake should be investigated. Clinical Trial Registry number: NCT05019989. Available at: https://clinicaltrials.gov/ search?cond=NCT05019989. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
