Post-diagnostic statin use and its association with cancer recurrence and mortality in breast cancer patients: a systematic review and meta-analysis

Abstract

Background: Statins are widely acknowledged for their application in patients with hypercholesterolemia to reduce cardiovascular morbidity and mortality. More recently, their potential to exert pleiotropic effects, particularly in impeding the proliferation of neoplastic cells, has attracted considerable attention. Prior studies have demonstrated that statins may mitigate cancer progression and micrometastasis. However, the benefits of statins in breast cancer have been inconclusive.

Objective: The aim of this meta-analysis was to evaluate the impact of statin use following a breast cancer diagnosis on breast cancer recurrence and mortality.

Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 30th May 2023. Hazard ratios (HR) were pooled using a random-effect model. The primary outcome of interest was the risk of breast cancer recurrence. The secondary outcomes included breast cancer-specific mortality and all-cause mortality.

Results: A total of 15 studies with 156 448 patients were included in the final analysis. The mean age of patients between statin users and non-users was 64.59 and 59.15 years, respectively. Statin use was associated with a reduction in the recurrence of breast cancer [HR 0.76, 95% confidence interval (CI): 0.67-0.87] compared with non-statin users. This trend was similar among lipophilic statin users (HR 0.73, 95% CI: 0.63-0.85) but not for hydrophilic statin users (HR 1.17, 95% CI: 0.82-1.68). Furthermore, statin users exhibited a lower risk of breast cancer mortality (HR 0.80, 95% CI: 0.66-0.96) but all-cause mortality (HR 0.82, 95% CI: 0.66-1.02) was comparable among both groups of patients. Conversely, lipophilic statins demonstrated a reduction in both all-cause mortality (HR 0.84, 95% CI: 0.75-0.93) and breast cancer mortality (HR 0.85, 95% CI: 0.74-0.99) compared to non-statin users.

Conclusion: Among patients with breast cancer, statin use post-diagnosis decreases the risk of breast cancer recurrence and breast cancer mortality. Furthermore, lipophilic statins exhibit an additional advantage of reduction in all-cause mortality.PROSPERO registration: CRD42022362011.

Keywords: Breast cancer; Cancer recurrence; Cardio-oncology; Lipophilic statins; Statin; Women's health.