Abstract
Introduction: Despite numerous investigations, variations in breast cancer (BC) risk across different ages at first pregnancy remain inconclusive. Thus, this meta-analysis aimed to clarify this association and provide a comprehensive evaluation of the evidence.
Study Design: A systematic review.
Methods: PubMed, Web of Science, and Scopus databases were systematically searched to identify observational studies published up to March 16, 2025, examining BC risk in relation to age at first pregnancy. Statistical analyses were performed using Stata 18 and Review Manager 5.4. Heterogeneity and potential sources were assessed using the I² statistic and meta-regression, respectively. Publication bias was also evaluated with Begg’s and Egger’s tests. Pooled effect sizes were expressed as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model.
Results: Of 15,586 identified records, 141 studies involving 1,045,983 participants met the inclusion criteria. The pooled RR of BC for age at first pregnancy≥20 years versus<20 years was 1.18 (95% CI: 1.09–1.28), and the pooled OR was 1.31 (95% CI: 1.26–1.37). Moreover, dose-response meta-analysis demonstrated a consistent upward trend, indicating that BC risk increases by 8–12% for every 5-year delay in the first pregnancy.
Conclusion: Our findings revealed that BC risk increases progressively with older age at first pregnancy. However, the overall evidence was moderate due to study limitations. Accordingly, further research is warranted to clarify underlying mechanisms and population-specific variations.