Postdiagnosis Statin Use and Breast Cancer Mortality

Importance: Emerging evidence suggests that cholesterol plays a role in breast cancer (BC) metabolism, raising the possibility that cholesterol-lowering medications, such as statins, may improve BC prognosis. Objective: To evaluate the association between postdiagnosis statin initiation and BC mortality using an emulated target trial approach. Design, Setting, and Participants: This observational cohort study using a target trial framework included 96 924 women diagnosed with stage I to III BC from 2000 to 2021 from Nationwide Danish registries, including the Danish Breast Cancer Group's clinical database and the Danish National Prescription Registry. Women with prior invasive BC or prediagnosis use of cholesterol-lowering medication were excluded. Eligible patients were duplicated into a cloned cohort and assigned to 1 of 2 treatment strategies: statin initiation within 36 months postdiagnosis or no statin initiation. Patients were followed up until deviation from the assigned strategy, emigration, death, 10 years of follow-up, or October 5, 2022. Exposures: Initiation of any statin within 36 months after BC diagnosis. Main Outcomes and Measures: The primary outcome was BC mortality. Secondary outcomes included all-cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using inverse probability of censoring weighted (IPCW) Cox regression models with a robust variance estimator. Results: A total of 66 952 patients with BC were enrolled in the emulated target trial (17 152 [27.6%] were aged 50-59 years); 4851 (7.2%) initiated statins within 36 months after diagnosis. Over 606 266 person-years of follow-up, 9130 patients died from BC and 19 679 from any cause. The 10-year risk of breast cancer mortality was 11.8% among statin initiators and 13.5% among noninitiators, corresponding to a risk difference of 1.7% (95% CI, 0.5% to 3.0%). A similar difference was observed for all-cause mortality (23.3% vs 24.5%; risk difference, 1.2%; 95% CI, -0.1% to 2.5%). IPCW analysis yielded an HR of 0.90 (95% CI, 0.85 to 0.95) for BC mortality and 0.92 (95% CI, 0.85 to 1.00) for all-cause mortality among statin initiators vs noninitiators. Conclusions and Relevance: In this cohort study, among 66 952 women with early BC, postdiagnosis statin initiation was associated with a modest reduction in BC and all-cause mortality. These findings support further investigation into the potential role of statins as an adjunct to standard adjuvant BC treatment.