Statin use and breast cancer survival: a nationwide cohort study from Finland.

Teemu J Murtola,Eero Pukkala,James M Wright,Kala Visvanathan,Harri Vainio,Miia Artama

doi:10.1371/journal.pone.0110231

Abstract

Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could delay or prevent breast cancer recurrence but the effect on disease-specific mortality remains unclear. We evaluated risk of breast cancer death among statin users in a population-based cohort of breast cancer patients. The study cohort included all newly diagnosed breast cancer patients in Finland during 1995–2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use before and after the diagnosis was obtained from a national prescription database. We used the Cox proportional hazards regression method to estimate mortality among statin users with statin use as time-dependent variable. A total of 4,151 participants had used statins. During the median follow-up of 3.25 years after the diagnosis (range 0.08–9.0 years) 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. After adjustment for age, tumor characteristics, and treatment selection, both post-diagnostic and pre-diagnostic statin use were associated with lowered risk of breast cancer death (HR 0.46, 95% CI 0.38–0.55 and HR 0.54, 95% CI 0.44–0.67, respectively). The risk decrease by post-diagnostic statin use was likely affected by healthy adherer bias; that is, the greater likelihood of dying cancer patients to discontinue statin use as the association was not clearly dose-dependent and observed already at low-dose/short-term use. The dose- and time-dependence of the survival benefit among pre-diagnostic statin users suggests a possible causal effect that should be evaluated further in a clinical trial testing statins’ effect on survival in breast cancer patients.

Highlights

Breast cancer is the leading cause of cancer death among women globally. [1] Experimental studies suggest that statins, a well-established group of cholesterol-lowering drugs, may have antitumor properties against this common cancer. [2–4].Statins reduce cholesterol biosynthesis in the liver by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway
Some recent studies have reported lowered overall cancer mortality among statin users, [9–13] including one study that reported decreased breast cancer mortality among prediagnostic statin users, [13] and other studies have suggested that statin use is associated with improved recurrence-free survival among breast cancer patients. [14–17] statins may exert a greater effect on cancer progression versus initiation
We have demonstrated lowered risk of breast cancer death among statin users in a nationwide cohort of all breast cancer patients diagnosed in Finland during a period of nine years

Summary

Introduction

Breast cancer is the leading cause of cancer death among women globally. [1] Experimental studies suggest that statins, a well-established group of cholesterol-lowering drugs, may have antitumor properties against this common cancer. [2–4].Statins reduce cholesterol biosynthesis in the liver by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway. [1] Experimental studies suggest that statins, a well-established group of cholesterol-lowering drugs, may have antitumor properties against this common cancer. This pathway produces isoprenoids that are critical for regulation of cell growth. There is no clear association between statin use and breast cancer incidence. Some recent studies have reported lowered overall cancer mortality among statin users, [9–13] including one study that reported decreased breast cancer mortality among prediagnostic statin users, [13] and other studies have suggested that statin use is associated with improved recurrence-free survival among breast cancer patients. [14–17] statins may exert a greater effect on cancer progression versus initiation. We studied the association between statin use and breast cancer mortality among breast cancer patients in a nationwide population-based cohort Some recent studies have reported lowered overall cancer mortality among statin users, [9–13] including one study that reported decreased breast cancer mortality among prediagnostic statin users, [13] and other studies have suggested that statin use is associated with improved recurrence-free survival among breast cancer patients. [14–17] statins may exert a greater effect on cancer progression versus initiation.

Methods

Results

Conclusion