Statin use and breast cancer-specific mortality and recurrence: a systematic review and meta-analysis including the role of immortal time bias and tumour characteristics.

BACKGROUND: The association between statins and breast cancer-specific mortality and recurrence has been examined in several previous observational studies and meta-analyses. However, potentially important effect modifiers have not often been explored in previous meta-analyses. In this study, an updated systematic review and meta-analysis was undertaken to ascertain the association between statins and both breast cancer death (BCD) and breast cancer recurrence (BCR). METHODS: Articles were sourced from various databases up until the 13th of June 2024, and effect estimates were pooled using the random effects model. Subgroup analyses were conducted by the potential for immortal time bias (ITB), type of statin (lipophilic vs hydrophilic), estrogen receptor status (positive vs negative), stage ('early' vs 'advanced'), and type of postdiagnostic use ('new' vs 'prevalent' user). RESULTS: Pooled results showed that there was a statistically significant protective association between statin use and both BCD (21 studies, hazard ratio = 0.81, 95% CI: 0.75-0.87) and BCR (20 studies, HR = 0.81, 95% CI: 0.74-0.89). Lipophilic statins were more protective than hydrophilic statins with BCD as the outcome, and there were suggestions of a more protective association in studies with ITB and in ER+ patients with BCR as the outcome. There was little evidence of effect modification by stage or type of postdiagnostic use. CONCLUSION: In this meta-analysis, we observed that statin use, particularly lipophilic statin use, was associated with favourable outcomes for BCD and BCR.