Abstract PD1-01: Impact of statin use on cancer recurrence and mortality in patients with breast cancer: A systematic review and meta-analysis

Abstract

Abstract Background: Statins have been described as having an association with a decreased risk of breast cancer. They have also shown antineoplastic properties in preclinical studies. Statins inhibit the enzyme 'HMG CoA reductase' and the expression of this enzyme in cancer cells has been implicated as an adverse prognostic factor in patients with breast cancer. Methods: We performed a systemic review of literature through April 2015 and utilized PubMed and Embase to identify studies that described an association between statin use and survival in breast cancer. Studies which did not report a comparison of survival using Kaplan-Meier curves were excluded. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated using the random effects model, and heterogeneity was measured using the inconsistency index (I2). Results: After reviewing 637 abstracts, 12 studies which included a total of 87951 patients were identified and data was extracted. 8 studies provided a summary statistic for the association of statins with recurrence-free survival (RFS) in patients with breast cancer and were included in a meta-analysis. Statin use was associated with improved RFS (N= 29729 patients, HR 0.66; 95% CI 0.53- 0.84) with moderate heterogeneity (I2= 48%). Furthermore, this survival benefit appeared to be confined to use of lipophilic statins (3 studies, HR 0.72; 95% CI 0.59- 0.89) as hydrophilic statin use was not associated with improvement in RFS (3 studies, HR 0.80; 95% CI 0.44- 1.46). A meta-analysis of 5 studies showed no significant association between the use of statins on breast cancer-specific survival (CSS) (N= 60686 patients, HR 0.71; 95% CI 0.49- 1.03, I2= 84%). We also found no association between statin use and overall survival (OS) (5 studies and 22283 patients, HR 0.83; 95% CI 0.58- 1.19, I2= 62%). Conclusions: Statin use, or more specifically, lipophilic statin use is associated with an improved recurrence-free survival for patients with breast cancer. However, there was no effect of statin use on either cancer-specific survival or overall survival. These benefits need to be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs will need to be identified. Characteristics of included studiesNameYearCountryImpact on RFSImpact on CSSImpact on OSSample SizeMedian follow-up (in years)Desai2015USANA0.59 [0.32, 1.06]NA7,88311.5Cardwell2015UKNA0.84 [0.68, 1.04]0.84 [0.72, 0.97]17,8805.7Murtola2014FinlandNA0.46 [0.38, 0.55]NA31,1143.25Boudreau2014USA0.78 [0.56, 1.08]NANA4,2166.3Sendur2014TurkeyP 0.004P 0.005P = 0.0051,1724Brewer2013USA0.49 [0.28-0.84]0.85 [0.46, 1.57]0.80 [0.43, 1.49]724NANickels2013Germany0.83 [0.54,1.24]0.89 [0.52, 1.49]1.21 [0.87, 1.69]3,085*5.3Zeichner2013USA1.42 [0.42, 4.81]NA1.5 [0.07, 32.02]3003.5Chae2011USA0.40 [0.24, 0.67]NANA7034.5Ceacareanu2011USA0.27 [0.10, 0.71]NA0.23 [0.08, 0.66]2942.5Ahern2011Denmark0.80 [0.64, 1.00]NANA18,7696.8Kwan2008USA0.67 [0.39, 1.13]NANA1,8115*= sample size for RFS: 2912, Abbreviations: RFS: recurrence-free survival, CSS: cancer-specific survival, OS: overall survival (expressed in hazard ratio and 95% confidence intervals) Citation Format: Manthravadi S, Shrestha A, Madhusudhana S. Impact of statin use on cancer recurrence and mortality in patients with breast cancer: A systematic review and meta-analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-01.