110MO - Statin use and early breast cancer survival: A Danish population-based cohort study using an emulated target trial approach

Background

Compelling evidence for the role of cholesterol in breast cancer metabolism suggests that cholesterol-lowering medications, such as statins, may improve breast cancer (BC) prognosis. We conducted a target trial to emulate a randomized trial of statin initiation in adjuvant BC patients using observational data.

Methods

We identified 110,160 female patients diagnosed with stage I, II, or III BC and registered in the clinical registry of the Danish Breast Cancer Group between 2000 and 2020. Women with prior invasive breast carcinoma or cholesterol-lowering therapy at diagnosis were excluded. To emulate a target trial of statin initiation after BC diagnosis, each eligible patient was duplicated into a cloned cohort and assigned to one of the two treatment strategies: initiate statins within 36 months of diagnosis or not to initiate statins. Patients were followed from date of diagnosis until deviation of the assigned strategy, emigration, death, or 1 October 2022. The primary endpoint was BC mortality. We used inverse-probability of censoring-weighting (IPCW) to estimate weights based on prognostic factors. We computed hazard ratios (HR) with 95% confidence intervals (CIs) of BC mortality in statin users vs. non-statin users. In secondary analyses, we used multivariable Cox regression models and conducted landmark analysis after 10 years of follow-up to estimate HR of BC mortality and 95% CIs.

Results

From the cloned cohort of 220,320 patients, we enrolled 133,904 BC patients, among whom 9,702 were statin users. The analysis using IPCW yielded a HR of 0.96 (95% CI: 0.91-1.01) for BC mortality in statin users vs. non-statin users. This finding was complemented by the results of the Cox regression (HR 0.81, 95% CI: 0.73-0.90) and the 10-year landmark analysis (HR 0.86, 95% CI: 0.76-0.98), both showing reduced BC mortality among statin users. Particularly among patients receiving adjuvant chemotherapy, statin users had lower risk of BC mortality compared to non-statin users (HR 0.94, 95% CI: 0.86-1.02; HR_cox 0.64, 95% CI: 0.52-0.79; HR_landmark 0.76, 95% CI: 0.58-1.00).

Conclusions

The results suggest a potential benefit of adding statins to standard adjuvant BC treatment, particularly in conjunction with chemotherapy.

Legal entity responsible for the study

The authors.

Funding

Director Michael Hermann Nielsen's Memorial Grant, Manufacturer Einar Willumsen's Memorial Grant, Astrid Thaysen's Grant for Medical Basic Research, Eva and Henry Frænkel's Memorial Fund, and Novo Nordisk Foundation.

Disclosure

All authors have declared no conflicts of interest.