The Effect of Diet on Breast Cancer Recurrence: The DIANA-5 Randomized Trial.

PURPOSE: The DIANA-5 randomized controlled trial assessed the effectiveness of a diet based on Mediterranean and macrobiotic traditions (macro-Mediterranean diet) in reducing breast cancer recurrence. PATIENTS AND METHODS: The DIANA-5 study involved 1,542 patients with breast cancer at high risk of recurrence because of estrogen receptor-negative cancer, or metabolic syndrome, or high plasma levels of insulin or testosterone. Women were randomly assigned to an active dietary intervention (IG) or a control group (CG). Both groups received the 2007 American Institute for Cancer Research/World Cancer Research Fund recommendations for cancer prevention. The intervention consisted of meetings with kitchen classes, community meals, and dietary recommendations. Recommended foods included whole grain cereals, legumes, soy products, vegetables, fruit, nuts, olive oil, and fish. Foods to be avoided were refined products, potatoes, sugar and desserts, red and processed meat, dairy products, and alcoholic drinks. A compliance Dietary Index was defined by the difference between recommended and discouraged foods. RESULTS: Over the 5 years of follow-up, 95 patients of the IG and 98 of the CG developed breast cancer recurrence [HR = 0.99; 95% confidence interval (CI): 0.69-1.40]. The analysis by compliance to the dietary recommendations (IG and CG together) showed that the women in the upper tertile of Dietary Index change had an HR of recurrence of 0.59 (95% CI: 0.36-0.92) compared with women in the lower tertile. CONCLUSIONS: The DIANA-5 dietary intervention trial failed to show a reduction in breast cancer recurrence, although self-reported diet at year 1 in IG and CG combined showed a protective association with the higher Dietary Index change. See related commentary by McTiernan, p. 931.

A Home-Treatment Algorithm Based on Anti-inflammatory Drugs to Prevent Hospitalization of Patients With Early COVID-19: A Matched-Cohort Study (COVER 2).

Background and Aim: While considerable success has been achieved in the management of patients hospitalized with severe coronavirus disease 2019 (COVID-19), far less progress has been made with early outpatient treatment. We assessed whether the implementation of a home treatment algorithm-designed based on a pathophysiologic and pharmacologic rationale-and including non-steroidal anti-inflammatory drugs, especially relatively selective cyclooxygenase-2 inhibitors and, when needed, corticosteroids, anticoagulants, oxygen therapy and antibiotics-at the very onset of mild COVID-19 symptoms could effectively reduce hospital admissions. Methods: This fully academic, matched-cohort study evaluated outcomes in 108 consecutive consenting patients with mild COVID-19, managed at home by their family doctors between January 2021 and May 2021, according to the proposed treatment algorithm and in 108 age-, sex-, and comorbidities-matched patients on other therapeutic schedules (ClinicalTrials.gov: NCT04854824). The primary outcome was COVID-19-related hospitalization. Analyses were by intention-to-treat. Results: One (0.9%) patient in the "recommended" cohort and 12 (11.1%) in the "control" cohort were admitted to hospital (P = 0.0136). The proposed algorithm reduced the cumulative length of hospital stays by 85% (from 141 to 19 days) as well as related costs (from €60.316 to €9.058). Only 9.8 patients needed to be treated with the recommended algorithm to prevent one hospitalization event. The rate of resolution of major symptoms was numerically-but not significantly-higher in the "recommended" than in the "control" cohort (97.2 vs. 93.5%, respectively; P = 0.322). Other symptoms lingered in a smaller proportion of patients in the "recommended" than in the "control" cohort (20.4 vs. 63.9%, respectively; P < 0.001), and for a shorter period. Conclusion: The adoption of the proposed outpatient treatment algorithm during the early, mild phase of COVID-19 reduced the incidence of subsequent hospitalization and related costs.

A simple, home-therapy algorithm to prevent hospitalisation for COVID-19 patients: A retrospective observational matched-cohort study.

BACKGROUND: Effective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system. METHODS: This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021 in Northern and Central Italy, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat. FINDINGS: All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the 'recommended schedule' cohort and 14 [7-30] days in the matched 'control' cohort (p = 0·033). Other symptoms persisted in a lower percentage of patients in the 'recommended' than in the 'control' cohort (23·3% versus 73·3%, respectively, p<0·0001) and for a shorter period (p = 0·0107). Two patients in the 'recommended' cohort were hospitalised compared to 13 (14·4%) controls (p = 0·0103). The prevention algorithm reduced the days and cumulative costs of hospitalisation by >90%. INTERPRETATION: Implementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but reduced the risk of hospitalisation and related treatment costs. Given the study design, additional research would be required to consolidate the proposed treatment recommendations. FUNDING: Fondazione Cav.Lav. Carlo Pesenti.

Adherence to WCRF/AICR cancer prevention recommendations and metabolic syndrome in breast cancer patients.

Metabolic syndrome (MetS), conventionally defined by the presence of at least three out of five dismetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol and high plasma glucose and triglycerides), has been associated with both breast cancer (BC) incidence and prognosis. We investigated the association between the prevalence of MetS and a score of adherence to the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) recommendations for the prevention of cancer in a cross-sectional study of BC patients. The DIet and ANdrogen-5 study (DIANA-5) for the prevention of BC recurrences recruited 2092 early stage BC survivors aged 35-70. At recruitment, all women completed a 24-hour food frequency and physical activity diary on their consumption and activity of the previous day. Using these diaries we created a score of adherence to five relevant WCRF/AICR recommendations. The prevalence ratios (PRs) and 95% confidence intervals (CIs) of MetS associated with the number of recommendations met were estimated using a binomial regression model. The adjusted PRs of MetS decreased with increasing number of recommendations met (p < 0.001). Meeting all the five recommendations versus meeting none or only one was significantly associated with a 57% lower MetS prevalence (95% CI 0.35-0.73). Our results suggest that adherence to WCRF/AICR recommendations is a major determinant of MetS and may have a clinical impact.

Metabolic syndrome and breast cancer prognosis.

Metabolic syndrome (MS), conventionally defined by the presence of at least three out of five dysmetabolic traits (abdominal obesity, hypertension, low plasma HDL-cholesterol, high plasma glucose and high triglycerides), has been associated with an increased risk of several age-related chronic diseases, including breast cancer (BC). This may have prognostic implications for BC survivors. 2,092 early stage BC survivors aged 35-70, recruited in eleven Italian centres 0-5 years after surgical treatment (1.74 years on average), were followed-up over 2.8 years on average for additional BC-related events, including BC-specific mortality, distant metastasis, local recurrences and contralateral BC. At recruitment, 20 % of the patients had MS. Logistic regression models were carried out to generate OR and 95 % confidence intervals (CI) for new BC events associated with MS, adjusting for baseline pathological prognostic factors. New BC events occurred in 164 patients, including 89 distant metastases. The adjusted ORs for women with MS versus women without any MS traits were 2.17 (CI 1.31-3.60) overall, and 2.45 (CI 1.24-4.82) for distant metastasis. The OR of new BC events for women with only one or two MS traits was 1.40 (CI 0.91-2.16). All MS traits were positively associated with new BC events, and significantly so for low HDL and high triglycerides. MS is an important prognostic factor in BC. As MS is reversible through lifestyle changes, interventions to decrease MS traits in BC patients should be implemented in BC clinics.