Umbrella review finds convincing evidence linking former smoking to increased breast cancer risk

BACKGROUND: Smoking, both active and passive, has been associated with an increased risk of numerous cancers worldwide, yet its impact on breast cancer remains a subject of debate. While many studies have explored the link between smoking and breast cancer risk, the findings have been inconsistent and often contradictory. To clarify the nature and strength of the association between smoking exposure (current, former, and passive) and breast cancer, we conducted an umbrella review of meta-analyses of observational studies (PROSPERO registration number: CRD42024610213). METHODS: We conducted a systematic literature search in PubMed, Scopus, and Web of Science from inception to October 24, 2024, and manually screened reference lists. Systematic reviews and meta-analyses of observational studies (cohort, case-control, and/or cross-sectional) examining the association between smoking (current, former, and passive) and breast cancer were included. Predefined evidence classification criteria were applied to assess the credibility of associations, graded as convincing (class I), highly suggestive (class II), suggestive (class III), weak (class IV), or no evidence (class V). Data were extracted for effect estimates, heterogeneity (I²), 95 % prediction intervals, small study effects, and excess significance bias, using random-effects models and AMSTAR 2 to evaluate methodological quality. FINDINGS: We identified 1095 articles, of which eight meta-analytic systematic reviews, encompassing 142 unique primary studies, were eligible for inclusion. These 142 articles provided data for six meta-analyses, covering former smoking, current smoking, and passive smoking (median cases = 1009; median population = 10,588). Convincing evidence (class I) was found for former smoking, with a summary relative risk (RR) of 1.13 (95 % CI 1.10-1.16). Highly suggestive evidence (class II) was observed for current smoking (RR 1.70, 95 % CI 1.66-1.74) and passive smoking (RR 1.53, 95 % CI 1.34-1.74). In our sensitivity analyses by study design, current smoking in cohort studies demonstrated a robust association with breast cancer risk (OR = 1.67, 95 % CI 1.62-1.71, Class II). Former smoking, analyzed in cohort studies, showed a modest but convincing association (OR = 1.10, 95 % CI 1.08-1.13, Class I), while in case-control studies, former smoking indicated a suggestive association with breast cancer risk (OR = 1.48, 95 % CI 1.19-1.82, Class III). CONCLUSION: Both former and current smoking, as well as passive exposure to smoke, were associated with an elevated risk of breast cancer. The association with former smoking may reflect long-lasting biological damage, while current and passive smoking likely act through similar carcinogenic pathways. Further studies are needed to establish causality and to account for potential confounding factors such as genetic predisposition and lifestyle. These findings highlight the importance of smoking cessation programs and stricter regulations on secondhand smoke to mitigate the global burden of breast cancer.