Statin use is associated with a lower risk of mortality in patients with malignant breast cancer treated with anthracyclines. A global federated health database analysis

Abstract Introduction Anthracyclines (ANT are a key component in the treatment of early breast cancer but are associated with an enhanced oxidative stress which is associated with f short- and long-term adverse events. Statins are a well-known class of lipid lowering agent with anti-inflammatory properties that could potentially counteract ANT toxicity in cancer patients. Purpose To assess the potential therapeutic benefit of statins among malignant breast cancer patients treated with ANT. Methods Retrospective study utilizing a global federated health research network (TriNetX). Patients with malignant breast cancer (ICD code C50) treated with ANT were categorized in two groups: statin users (at least 1 month before the ANT treatment); and non-statin users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the intra-treatment (within 6 months), post-treatment (6 months-1 year) and long-term (1 year-5 years) risk of-all cause death. A further sensitivity analysis was done to assess the risk differences between hydrophilic (rosuvastatin and pravastatin) and lipophilic (atorvastatin, simvastatin, lovastatin) statins. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Results Amongst the 36,770 patients with breast cancer identified (mean age 60±12.6 years, 98.6% female): 6,616 (17.9%) were statin users and 30,154 (81.1%) were non-statin users. Statins users were older and had more cardiovascular risk factors. After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.72, 95%CI 0.63-0.83) compared to non-statins users. Analyzing the different time frames, the lowest risk of all-cause death was observed in the early period after the ATN treatment (Figure 1). The 5-year all-cause death was reduced in both the hydrophilic (HR: 0.69, 95%CI 0.58-0.83) and lipophilic statins (HR 0.72, 95%CI 0.65-0.79), when compared to non-statins users (Figure 2), with no significant differences between these two statin types (p=0.496). Conclusion Statin use was associated with a reduced risk of all-cause death in breast cancer patients treated with ATN. Further studies are needed to clarify the mechanism(s) by which statins counteract the ATN toxicity.