The Role of the Mediterranean Diet in Breast Cancer Survivorship: A Systematic Review and Meta-Analysis of Observational Studies and Randomised Controlled Trials

Abstract

Female breast cancer is the most frequently diagnosed cancer. The long-term survival rates for this disease have increased; however, the unique demand for high-quality healthcare to improve breast-cancer survivorship are commonly unmet. The Mediterranean diet (MD) is associated with reduced breast-cancer risk and various health-related benefits in the general population, but its effect on breast-cancer survivors remains uncertain. The objective of this systematic review and meta-analysis was to assess current evidence from randomised controlled trials (RCTs) and observational studies (cohort, cross-sectional and case-control) regarding the effect of the MD on survival, quality of life (QoL) and health-related outcomes in female breast-cancer survivors. MEDLINE, EMBASE, Web of Science and the Cochrane library were searched for studies published before and including April 2022. Two reviewers independently screened the literature and completed the data extraction and risk-of-bias assessment. Eleven studies (fifteen reports) were included, including two RCTs, four cohort and five cross-sectional studies. The meta-analysis of the cohort studies showed strong evidence of an inverse association between high adherence to the MD and all-cause mortality (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.66-0.93, I²: 0%, Grading of Recommendations Assessment, Development and Evaluation (GRADE) = low certainty of evidence) and non-breast-cancer mortality (HR 0.67, 95% CI 0.50-0.90, I²: 0%, GRADE = very low certainty of evidence). The associations between high adherence to the MD and QoL and health-related parameters were not consistent. These findings highlight the potential of adherence to the MD to reduce the risk of mortality. Future research with better study designs, as well as more consistent measurements of QoL and MD adherence, taking into account changes in MD adherence over time and population subgroups, is needed to provide more robust evidence on the survival, QoL and health-related outcomes in BC survivors.

Keywords: Mediterranean diet; breast cancer; mortality; quality of life; survivorship; systematic review.

Figure 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram.

Figure 2

Summary of the evidence (harvest plot) from all the included studies (n = 11) for the associations between MD and reported outcomes. BC: breast cancer; BMI: body-mass index; HDL-C: high-density-lipoprotein cholesterol; HOMA-IR: Homeostatic Model Assessment of Insulin Resistance; QoL: quality of life; TAG: triacylglycerol; TC: total cholesterol; LDL-C: low-density-lipoprotein cholesterol. In each bar graph in the matrix, the heights of the bars indicate designs of included studies (high: RCT, medium: cohort study, low: cross-sectional study) and the colours of the bars indicate whether the results of the study were included in the meta-analysis (grey: included in meta-analyses, black: not included in meta-analyses). The rows of the matrix indicate the detected associations (positive, none or negative) between MD adherence and the outcomes reported by each study. The columns of the matrix indicate the outcomes reported by the included studies. † Breast-cancer subscales of FACT-B scale. * Subscales of EORTC QLQ-BR23 scale. ** The overall score for FACT-G or EQ-5D-3L. ‡ The Global Health Status/QoL subscale of EORTC QLQ-C30 scale. ∧ Subscales of EORTC QLQ-C30 scale.

Figure 3

Meta-analyses of MD adherence and (a) all-cause mortality (minimally adjusted), (b) all-cause mortality (maximally adjusted), (c) BC mortality (medium adjusted), (d) non-BC mortality (medium adjusted). IV: Weights are from fixed-effects model. DL: Weights are from random-effects model. MD: Mediterranean diet [19,36,37].

Figure 4

Meta-analysis of MD adherence and BMI (kg/m²) (fixed-effects model) [42,44,45,49].