Skip to main content
Top
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Statin use and breast cancer survival: a nationwide cohort study in Scotland

Authors: Úna C. Mc Menamin, Liam J. Murray, Carmel M. Hughes, Chris R. Cardwell

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Preclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality.

Methods

We conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin.

Results

A total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose–response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98).

Conclusion

Overall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer.
Literature
1.
go back to reference Chan KK, Oza AM, Siu LL. The statins as anticancer agents. Clin Cancer Res. 2003;9:10–9.PubMed Chan KK, Oza AM, Siu LL. The statins as anticancer agents. Clin Cancer Res. 2003;9:10–9.PubMed
2.
go back to reference Gauthaman K, Fong CY, Bongso A. Statins, stem cells, and cancer. J Cell Biochem. 2009;106:975–83.CrossRefPubMed Gauthaman K, Fong CY, Bongso A. Statins, stem cells, and cancer. J Cell Biochem. 2009;106:975–83.CrossRefPubMed
3.
go back to reference Gopalan A, Yu W, Sanders BG, Kline K. Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 signaling pathway. Cancer Lett. 2013;329:9–16.CrossRefPubMed Gopalan A, Yu W, Sanders BG, Kline K. Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 signaling pathway. Cancer Lett. 2013;329:9–16.CrossRefPubMed
4.
go back to reference Vainio P, Lehtinen L, Mirtti T, et al. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011;2:1176–90.CrossRefPubMedPubMedCentral Vainio P, Lehtinen L, Mirtti T, et al. Phospholipase PLA2G7, associated with aggressive prostate cancer, promotes prostate cancer cell migration and invasion and is inhibited by statins. Oncotarget. 2011;2:1176–90.CrossRefPubMedPubMedCentral
5.
go back to reference Campbell MJ, Esserman LJ, Zhou Y, et al. Breast Cancer Growth Prevention by Statins Breast Cancer Growth Prevention by Statins. Cancer Res. 2006;66:8707–14.CrossRefPubMed Campbell MJ, Esserman LJ, Zhou Y, et al. Breast Cancer Growth Prevention by Statins Breast Cancer Growth Prevention by Statins. Cancer Res. 2006;66:8707–14.CrossRefPubMed
6.
go back to reference Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Ghosh CG. Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal. 2010;22:749–58.CrossRefPubMedPubMedCentral Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Ghosh CG. Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal. 2010;22:749–58.CrossRefPubMedPubMedCentral
7.
go back to reference Garwood ER, Kumar AS, Baehner FL, et al. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res Treat. 2010;119:137–44.CrossRefPubMedPubMedCentral Garwood ER, Kumar AS, Baehner FL, et al. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res Treat. 2010;119:137–44.CrossRefPubMedPubMedCentral
8.
go back to reference Bjarnadottir O, Romero Q, Bendahl P-O, et al. Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial. Breast Cancer Res Treat. 2013;138:499–508.CrossRefPubMed Bjarnadottir O, Romero Q, Bendahl P-O, et al. Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial. Breast Cancer Res Treat. 2013;138:499–508.CrossRefPubMed
9.
go back to reference Bjarnadottir O, Kimburg S, Johansson I, et al. Global transcriptional chages following statin treatment in breast cancer. Clin Cancer Res. 2015;21:3402–11.CrossRefPubMed Bjarnadottir O, Kimburg S, Johansson I, et al. Global transcriptional chages following statin treatment in breast cancer. Clin Cancer Res. 2015;21:3402–11.CrossRefPubMed
10.
go back to reference Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Eng J Med. 2012;367:1792–802.CrossRef Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Eng J Med. 2012;367:1792–802.CrossRef
11.
go back to reference Murtola TJ, Visvanathan K, Artama M, Vainio H, Pukkala E. Statin use and breast cancer survival: a nationwide cohort study from Finland. PLoS ONE. 2014;9, e110231.CrossRefPubMedPubMedCentral Murtola TJ, Visvanathan K, Artama M, Vainio H, Pukkala E. Statin use and breast cancer survival: a nationwide cohort study from Finland. PLoS ONE. 2014;9, e110231.CrossRefPubMedPubMedCentral
12.
go back to reference Chubak J, Boudreau DM, Wirtz HS, McKnight B, Weiss NS. Threats to Validity of Nonrandomized Studies of Postdiagnosis Exposures on Cancer Recurrence and Survival. J Natl Cancer Inst. 2013;105(19):1456–62.CrossRefPubMedPubMedCentral Chubak J, Boudreau DM, Wirtz HS, McKnight B, Weiss NS. Threats to Validity of Nonrandomized Studies of Postdiagnosis Exposures on Cancer Recurrence and Survival. J Natl Cancer Inst. 2013;105(19):1456–62.CrossRefPubMedPubMedCentral
13.
go back to reference Tamim H, Monfared AALJ. Application of lag-time into exposure definitions to control for protopathic bias. Pharmacoepidemiol Drug Saf. 2007;16:250–8.CrossRefPubMed Tamim H, Monfared AALJ. Application of lag-time into exposure definitions to control for protopathic bias. Pharmacoepidemiol Drug Saf. 2007;16:250–8.CrossRefPubMed
14.
go back to reference Cardwell CR, Hicks BM, Hughes CML. Statin use after diagnosis of breast cancer and survival: a population-based cohort study. Epidemiology. 2015;26:68–78.CrossRefPubMed Cardwell CR, Hicks BM, Hughes CML. Statin use after diagnosis of breast cancer and survival: a population-based cohort study. Epidemiology. 2015;26:68–78.CrossRefPubMed
15.
go back to reference Ahern TP, Pedersen L, Tarp M, et al. Statin prescriptions and breast cancer recurrence risk: A Danish nationwide prospective cohort study. J Natl Cancer Inst. 2011;103:1461–8.CrossRefPubMedPubMedCentral Ahern TP, Pedersen L, Tarp M, et al. Statin prescriptions and breast cancer recurrence risk: A Danish nationwide prospective cohort study. J Natl Cancer Inst. 2011;103:1461–8.CrossRefPubMedPubMedCentral
16.
go back to reference Boudreau DM, Yu O, Chubak J, Wirtz HS, Bowles EJ, Fujii M, et al. Comparative safety of cardiovascular medication use and breast cancer outcomes among women with early stage breast cancer. Breast Cancer Res Treat. 2014;144:405–16.CrossRefPubMedPubMedCentral Boudreau DM, Yu O, Chubak J, Wirtz HS, Bowles EJ, Fujii M, et al. Comparative safety of cardiovascular medication use and breast cancer outcomes among women with early stage breast cancer. Breast Cancer Res Treat. 2014;144:405–16.CrossRefPubMedPubMedCentral
17.
go back to reference Kwan ML, Habel LA, Flick ED, Quesenberry CP, Caan B. Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Res Treat. 2008;109:573–9.CrossRefPubMed Kwan ML, Habel LA, Flick ED, Quesenberry CP, Caan B. Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors. Breast Cancer Res Treat. 2008;109:573–9.CrossRefPubMed
18.
go back to reference Chae YK, Valsecchi ME, Kim J, et al. Reduced Risk of Breast Cancer Recurrence in Patients Using ACE Inhibitors, ARBs, and/or Statins. Cancer Invest. 2011;29:585–93.CrossRefPubMed Chae YK, Valsecchi ME, Kim J, et al. Reduced Risk of Breast Cancer Recurrence in Patients Using ACE Inhibitors, ARBs, and/or Statins. Cancer Invest. 2011;29:585–93.CrossRefPubMed
19.
go back to reference Lévesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies : example using statins for preventing progression of diabetes. BMJ. 2010;340:907–11.CrossRef Lévesque LE, Hanley JA, Kezouh A, Suissa S. Problem of immortal time bias in cohort studies : example using statins for preventing progression of diabetes. BMJ. 2010;340:907–11.CrossRef
20.
go back to reference Ahern TP, Lash TL, Damkier P, Christiansen PM, Cronin-Fenton DP. Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncol. 2014;15:e461–8.CrossRefPubMedPubMedCentral Ahern TP, Lash TL, Damkier P, Christiansen PM, Cronin-Fenton DP. Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncol. 2014;15:e461–8.CrossRefPubMedPubMedCentral
21.
go back to reference British Medical Association and the Royal Pharmaceutical Society of Great Britain. British National Formulary.http://www bnf org/bnf/index htm 2013 British Medical Association and the Royal Pharmaceutical Society of Great Britain. British National Formulary.http://​www bnf org/bnf/index htm 2013
22.
go back to reference Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the furture of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the furture of TNM. Ann Surg Oncol. 2010;17:1471–4.CrossRefPubMed
23.
go back to reference Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–94.CrossRefPubMed Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–94.CrossRefPubMed
24.
go back to reference The Scottish Government. Scottish Index of Multiple Deprivation 2009: General Report. Edinburgh: A Scottish Government National Statistics Publication; 2009. The Scottish Government. Scottish Index of Multiple Deprivation 2009: General Report. Edinburgh: A Scottish Government National Statistics Publication; 2009.
25.
go back to reference Zhou Z, Rahme E, Abrahamowicz M, Pilote L. Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol. 2005;162(10):1016–23.CrossRefPubMed Zhou Z, Rahme E, Abrahamowicz M, Pilote L. Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. Am J Epidemiol. 2005;162(10):1016–23.CrossRefPubMed
26.
27.
28.
go back to reference Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef
29.
go back to reference Wang A, Aragaki AK, Tang JY et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Br J Cancer 2016; Jun 9 [Epub ahead of print]. Wang A, Aragaki AK, Tang JY et al. Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Br J Cancer 2016; Jun 9 [Epub ahead of print].
30.
31.
go back to reference Desai P, Lehman A, Chlebowski RT, et al. Statins and breast cancer stage and mortality in the Women’s Health Initiative. Cancer Causes Control. 2015;26:529–39.CrossRefPubMedPubMedCentral Desai P, Lehman A, Chlebowski RT, et al. Statins and breast cancer stage and mortality in the Women’s Health Initiative. Cancer Causes Control. 2015;26:529–39.CrossRefPubMedPubMedCentral
32.
go back to reference Nickels S, Vrieling A, Seibold P, et al. Mortality and recurrence risk in relation to the use of lipid-lowering drugs in a prospective breast cancer patient cohort. PLoS ONE. 2013;8, e75088.CrossRefPubMedPubMedCentral Nickels S, Vrieling A, Seibold P, et al. Mortality and recurrence risk in relation to the use of lipid-lowering drugs in a prospective breast cancer patient cohort. PLoS ONE. 2013;8, e75088.CrossRefPubMedPubMedCentral
33.
go back to reference Kumar AS, Benz CC, Shim V, Minami CA, Moore DH, Esserman LJ. Estrogen Receptor-Negative Breast Cancer Is Less Likely to Arise among Lipophilic Statin Users. Cancer Epidemiol Biomarkers Prev. 2008;17:1028–33.CrossRefPubMed Kumar AS, Benz CC, Shim V, Minami CA, Moore DH, Esserman LJ. Estrogen Receptor-Negative Breast Cancer Is Less Likely to Arise among Lipophilic Statin Users. Cancer Epidemiol Biomarkers Prev. 2008;17:1028–33.CrossRefPubMed
34.
go back to reference Sarfati D, Blakely T, Pearce N. Measuring cancer survival in populations: relative survival vs. cancer-specific survival. Int J Epidemiol. 2010;39:598–610.CrossRefPubMed Sarfati D, Blakely T, Pearce N. Measuring cancer survival in populations: relative survival vs. cancer-specific survival. Int J Epidemiol. 2010;39:598–610.CrossRefPubMed
35.
go back to reference Stewart D, Cunningham ITS, Hansford D, John D, McCaig D, McLay J. General practitioners’ views and experiences of over-the-counter simvastatin in Scotland. Br J Clin Pharmacol. 2010;70:356–9.CrossRefPubMedPubMedCentral Stewart D, Cunningham ITS, Hansford D, John D, McCaig D, McLay J. General practitioners’ views and experiences of over-the-counter simvastatin in Scotland. Br J Clin Pharmacol. 2010;70:356–9.CrossRefPubMedPubMedCentral
36.
go back to reference Yang Y, Pharmd SH, Propert K, Hwang W, Sarkar M, Lewis JD. Chronic statin therapy and the risk of colorectal cancer. Pharmacoepidemiol Drug Saf. 2008;17:869–76.CrossRefPubMed Yang Y, Pharmd SH, Propert K, Hwang W, Sarkar M, Lewis JD. Chronic statin therapy and the risk of colorectal cancer. Pharmacoepidemiol Drug Saf. 2008;17:869–76.CrossRefPubMed
37.
go back to reference Yood MU, Campbell UB, Rothman KJ, Jick SS, Lang J, et al. Using prescription claims data for drugs available over-the-counter (OTC). Pharmacoepidemiol Drug Saf. 2007;16(9):961–8.CrossRefPubMed Yood MU, Campbell UB, Rothman KJ, Jick SS, Lang J, et al. Using prescription claims data for drugs available over-the-counter (OTC). Pharmacoepidemiol Drug Saf. 2007;16(9):961–8.CrossRefPubMed
Metadata
Title
Statin use and breast cancer survival: a nationwide cohort study in Scotland
Authors
Úna C. Mc Menamin
Liam J. Murray
Carmel M. Hughes
Chris R. Cardwell
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2651-0

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine