Breast cancer determinants in low- to upper-middle-income countries: an umbrella review of meta-analyses of observational studies and an urgent call for implementation science

Abstract

Introduction: Meta-analyses on breast cancer determinants in low- and middle-income countries (LMICs), including upper-middle-income countries (UMICs), often produce fragmented, context-specific findings. This umbrella review provides a consolidated synthesis to identify consistent risk factors and strengthen the evidence base for guiding targeted public health strategies.

Methods and materials: In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic search for meta-analyses across multiple databases. Study quality was assessed using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tool. Data were analyzed using STATA version 14, applying a random-effects model to estimate pooled effect sizes with 95% confidence intervals. Forest plots were used to visualize determinants. Publication bias was assessed through funnel plots and Egger's test, while heterogeneity was evaluated using the I-squared (I²) statistic and Galbraith plots. Sensitivity analysis was performed to assess small-study effects.

Results: Out of 1,515 publications reviewed, 35 met the inclusion criteria. Eight determinants of breast cancer showed convincing evidence under the random-effects model: being overweight (POR = 1.16, 95% CI: 1.09-1.23), oral contraceptive use (POR = 1.19, 95% CI: 1.11-1.27), family history of breast cancer (POR = 2.26, 95% CI: 1.84-2.67), age ≥ 40 years (POR = 1.82, 95% CI: 1.60-2.05), smoking history (POR = 1.22, 95% CI: 1.11-1.34), exposure to air pollution (POR = 1.03, 95% CI: 1.01-1.05), higher fruit and vegetable consumption (POR = 0.82, 95% CI: 0.71-0.92), and history of night work (POR = 1.14, 95% CI: 1.02-1.25).

Conclusions: This umbrella review identified eight key breast cancer risk factors. Non-modifiable factors like age ≥ 40 and family history, along with modifiable factors such as overweight, smoking, oral contraceptive use, air pollution, and night shift work, increased the odds of breast cancer. Adequate fruit and vegetable intake was linked to reduced odds, suggesting a protective effect. We recommend that public health strategies promote healthy lifestyles and target high-risk groups through early screening and awareness campaigns, using evidence-based interventions to reduce the breast cancer burden.

Keywords: Breast cancer; Determinants; Low- and middle-income countries; Umbrella review; Upper-middle-income countries.

Fig. 1

PRISMA flow diagram showing the literature search, screening, and selection process for studies included in the umbrella review

Fig. 2

Funnel plot showing the 95% confidence limits for the determinants of breast cancer in low to upper-middle-income countries (n = 35), 2025

Fig. 3

Egger’s test results for detecting publication bias in studies on the determinants of breast cancer in low to upper-middle-income countries (n = 35), 2025

Fig. 4

Galbraith plot illustrating heterogeneity in the umbrella review of meta-analyses of observational studies on the determinants of breast cancer in low to upper-middle-income countries

Fig. 5

Sensitivity analysis showing no outlier studies among the included articles estimating the pooled determinants of breast cancer, 2025 (n = 35)

Fig. 6

A through D illustrates selected determinants of breast cancer identified in the umbrella review (n = 35). E through H, illustrates the determinants of breast cancer identified in Umbrella Review, 2024 (n = 35)