Statin Use, Cholesterol Level, and Mortality among Females with Breast Cancer

Abstract

Importance: Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level. Objective: To investigate the association between serum cholesterol, statin use, and BC mortality. Design, Setting, and Participants: This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022. Exposure: Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis. Main Outcomes and Measures: Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015. Results: A total of 13378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P =.03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P =.05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P =.001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P =.30). Reduced BC mortality among statin users was also observed in females with estrogen receptor-positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P =.03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P