Statin use may reduce mortality in early breast cancer

The addition of statins to standard adjuvant breast cancer treatment, particularly in combination with chemotherapy, appears to improve patient survival, suggests a study presented at ESMO Breast Cancer 2024.

“Compelling evidence for the role of cholesterol in breast cancer metabolism suggests that cholesterol-lowering medications, such as statins, may improve breast cancer prognosis,” said lead author Dr Sixten Harborg from the Aarhus University and Aarhus University Hospital, Aarhus, Denmark.

Harborg and colleagues then conducted a target trial emulating a randomized trial of statin initiation in adjuvant breast cancer patients using observational data.

A total of 110,160 female patients diagnosed with stage I, II, or III breast cancer in the clinical registry of the Danish Breast Cancer Group between 2000 and 2020 were identified. Those with prior invasive breast carcinoma or cholesterol-lowering therapy at diagnosis were excluded.

To emulate a randomized trial, eligible patients were duplicated into a cloned cohort and assigned to one of the two treatment regimens: use statins within 3 years of diagnosis or do not use statins. Participants were followed from the date of diagnosis until deviation of the assigned strategy, emigration, death, or 1 October 2022. Breast cancer mortality was the primary endpoint.

Inverse-probability of censoring-weighting (IPCW) was used to measure weights based on prognostic factors. Harborg and colleagues estimated the hazard ratios (HRs) with 95 percent confidence intervals (CIs) of the primary endpoint in statin users and nonusers. In secondary analyses, they computed the HR using multivariate Cox regression models and performed landmark analysis after 10 years of follow-up.

The cloned cohort consisted of 220,320 breast cancer patients, of whom 133,904 were included in the analysis. Of these, 9,702 initiated statins. [ESMO Breast Cancer 2024, abstract 110MO]

Reduced mortality

In the analysis using IPCW, statin users had a 4-percent lower risk of breast cancer mortality (HR, 0.96, 95 percent CI, 0.91‒1.01) than nonusers. This survival benefit persisted in the Cox regression (HR, 0.81, 95 percent CI, 0.73‒0.90) and the 10-year landmark analysis (HR, 0.86, 95 percent CI, 0.76‒0.98), both demonstrating reduced mortality among statin users.

Notably, the addition of statin to adjuvant chemotherapy resulted in a lower risk of breast cancer mortality when compared to no statins (target trial: HR, 0.94, 95 percent CI, 0.86‒1.02; Cox regression: HR, 0.64, 95 percent CI, 0.52‒0.79; landmark analysis: HR, 0.76, 95 percent CI, 0.58‒1.00).

“The results suggest a potential benefit of adding statins to standard adjuvant breast cancer treatment, particularly in conjunction with chemotherapy,” Harborg said.

These findings also “encourage the continuous effort of the MASTER study, a randomized, multicentre, double-blind, placebo-controlled comparison of standard adjuvant therapy plus placebo versus standard adjuvant therapy plus atorvastatin in patients with early breast cancer,” Harborg added.

Statins, the most common cholesterol-lowering drug, block the rate-limiting step in cholesterol biosynthesis and have anti-inflammatory effects. On the other hand, cholesterol is essential in cell membrane synthesis. [Borgquist, et al, JCO 2017; Ahern, et al, Lancet Oncology 2014]