Association of cesarean section with breast cancer: A systematic review and meta-analysis

Breast cancer (BC) remains the most prevalent malignancy among women globally, and its potential associations with reproductive factors have been extensively investigated. Among these, the role of the cesarean section (CS) as a potential risk factor has garnered increasing attention. The present systematic review aimed to evaluate the association between CS and BC risk, as well as its prognostic implications. A comprehensive literature search was conducted following Systematic Reviews and Meta-Analyses (PRISMA) guidelines across multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar. Four studies, comprising a total of 1,492,962 women, met the inclusion criteria and were analyzed. The findings revealed inconsistent results regarding the relationship between CS and BC risk. A nationwide cohort study from Korea reported a higher incidence of postpartum BC among women with a history of CS compared with those with vaginal deliveries, particularly in women of advanced maternal age. Conversely, a large population-based cohort study from Israel found no significant difference between CS and vaginal delivery groups in terms of BC incidence. In addition, retrospective cohort studies from Turkey indicated that patients with BC with a history of CS were diagnosed at a younger age and exhibited more aggressive tumor characteristics, including lymphovascular invasion and extracapsular extension. A meta-analysis was also performed, demonstrating a modest but statistically significant increased risk of BC incidence among women with a history of CS [odds ratio (OR)=1.26, 95% confidence interval (CI): 1.07-1.47], as well as a stronger association with extracapsular extension (OR=2.11, 95% CI: 1.42-3.15), but not with lymphovascular invasion (OR=1.63, 95% CI: 0.69-3.89). Proposed mechanisms underlying the potential link include hormonal alterations, increased fetal microchimerism, inflammation and metabolic disturbances associated with CS. However, discrepancies between studies may arise from variations in methodology, population characteristics and confounding factors. Given the current inconclusive evidence, clinical decision-making should prioritize maternal and neonatal safety while acknowledging potential long-term health implications. Further large-scale prospective studies are warranted to elucidate the biological mechanisms and clarify the association between CS and BC.