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Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

A Letter to the Editor to this article was published on 04 July 2019

Abstract

Introduction

The use of statins has been associated with improved survival in patients with breast cancer in several studies but results have been mixed. This study evaluates the impact of duration of statin use on breast cancer patient outcomes.

Methods

This is a single-institution, retrospective cohort, examining the impact of statin use on the outcomes of 1523 women diagnosed with operable breast cancer between1995 and 2015. Clinical variables were compared using Student’s t test, Fisher’s exact and Chi square tests. Overall (OS) and disease-free (DFS) survival were performed using Kaplan–Meier and Cox-Proportional Hazard (Cox-PH) analysis in the statistical software R.

Results

Patients were grouped by duration of statin use: never-statin user [N] (n = 1092), short (< 3 years) [S] (n = 115), moderate [M] (3–5 years) (n = 109) and long [L] (> 5 years) (n = 207) term. Over a median follow-up of 70.2 months, 138 women died (84 died of breast cancer) and 125 had disease recurrence. On multivariable Cox-PH analysis adjusting for clinical variables including metabolic comorbidities using the Charlson comorbidity index, OS in the [S] and [M] subgroups did not differ [N], while OS was improved in [L] (adjusted hazard ratio (AHR) 0.38, confidence interval (CI) 0.17–0.85, p < 0.018). DFS was also significantly improved in the [L] subgroup (adjusted HR 0.15, CI 0.05–0.48, p < 0.001). Subanalysis stratified by receptor status showed a trend towards improved DFS in all tumor subtypes including triple-negative breast cancer.

Conclusions

Our retrospective analyses suggest that long-term statin use (> 5 years) was associated with improved OS and DFS in women with breast cancer regardless of receptor subtype, even after adjusting for metabolic comorbidities.

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References

  1. WHO (2016) Breast cancer: prevention and control. WHO, Geneva

    Google Scholar 

  2. Keyomarsi K, Sandoval L, Band V, Pardee AB (1991) Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 51:3602–3609

    CAS  PubMed  Google Scholar 

  3. Agarwal B, Bhendwal S, Halmos B et al (1999) Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res 5:2223–2229

    CAS  PubMed  Google Scholar 

  4. Padayatty SJ, Marcelli M, Shao TC, Cunningham GR (1997) Lovastatin-induced apoptosis in prostate stromal cells. J Clin Endocrinol Metab 82:1434–1439. https://doi.org/10.1210/jcem.82.5.3960

    Article  CAS  PubMed  Google Scholar 

  5. Kusama T, Mukai M, Iwasaki T et al (2001) Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. Cancer Res 61:4885–4891

    CAS  PubMed  Google Scholar 

  6. Seeger H, Wallwiener D, Mueck A (2003) Statins can inhibit proliferation of human breast cancer cells in vitro. Exp Clin Endocrinol Diabetes 111:47–48. https://doi.org/10.1055/s-2003-37501

    Article  CAS  PubMed  Google Scholar 

  7. Ghosh-Choudhury NN, Mandal CC, Ghosh-Choudhury NN et al (2010) Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit breast cancer cell growth. Cell Signal 22:749–758. https://doi.org/10.1016/j.cellsig.2009.12.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Campbell MJ, Esserman LJ, Zhou Y et al (2006) Breast cancer growth prevention by statins. Cancer Res 66:8707–8714

    Article  CAS  PubMed  Google Scholar 

  9. Endo A (2010) A historical perspective on the discovery of statins. Proc Jpn Acad Ser B 86:484–493. https://doi.org/10.2183/pjab.86.484

    Article  CAS  Google Scholar 

  10. Nair PK, Mulukutla SR, Marroquin OC (2010) Stents and statins: history, clinical outcomes and mechanisms. Expert Rev Cardiovasc Ther 8:1283–1295. https://doi.org/10.1586/erc.10.113

    Article  CAS  PubMed  Google Scholar 

  11. Wiviott SD, Cannon CP, Morrow DA et al (2005) Can low-density lipoprotein be too low? the safety and efficacy of achieving very low low-density lipoprotein with intensive statin Therapy. J Am Coll Cardiol 46:1411–1416. https://doi.org/10.1016/j.jacc.2005.04.064

    Article  CAS  PubMed  Google Scholar 

  12. Ahern TP, Lash TL, Damkier P et al (2014) Statins and breast cancer prognosis: evidence and opportunities. Lancet Oncol 15:461–468. https://doi.org/10.1016/S1470-2045(14)70119-6

    Article  CAS  Google Scholar 

  13. Murtola TJ, Visvanathan K, Artama M et al (2014) Statin use and breast cancer survival: a nationwide cohort study from Finland. PLoS ONE 9:e110231. https://doi.org/10.1371/journal.pone.0110231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cardwell CR, Hicks BM, Hughes CML, Murray LJ (2015) Statin use after diagnosis of breast cancer and survival: a population-based cohort study. Epidemiology 26:68–78. https://doi.org/10.1097/EDE.0000000000000189

    Article  PubMed  Google Scholar 

  15. Sakellakis M, Akinosoglou K, Kostaki A et al (2016) Statins and risk of breast cancer recurrence. Breast Cancer. 8:199–205. https://doi.org/10.2147/BCTT.S116694

    Article  PubMed  Google Scholar 

  16. Nielsen SF, Nordestgaard BG, Bojesen SE (2012) Statin use and reduced cancer-related mortality. N Eng J Med 367:1792–1802. https://doi.org/10.1056/NEJMoa1201735

    Article  CAS  Google Scholar 

  17. Wang A, Aragaki AK, Tang JY et al (2016) Statin use and all-cancer survival: prospective results from the Women’s Health Initiative. Br J Cancer 115:129–135. https://doi.org/10.1038/bjc.2016.149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ahern TP, Pedersen L, Tarp M et al (2011) Statin prescriptions and breast cancer recurrence risk: a Danish nationwide prospective cohort study. J Natl Cancer Inst 103:1461–1468. https://doi.org/10.1093/jnci/djr291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Borgquist S, Giobbie-Hurder A, Ahern TP et al (2017) Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 Study. J Clin Oncol 35:1179–1188. https://doi.org/10.1200/JCO.2016.70.3116

    Article  CAS  PubMed  Google Scholar 

  20. Boudreau DM, Yu O, Chubak J et al (2014) Comparative safety of cardiovascular medication use and breast cancer outcomes among women with early stage breast cancer. Breast Cancer Res Treat 144:405–416. https://doi.org/10.1007/s10549-014-2870-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Desai P, Chlebowski R, Cauley JA et al (2013) Prospective analysis of association between statin use and breast cancer risk in the women’s health initiative. Cancer Epidemiol Biomark Prev 22:1868–1876. https://doi.org/10.1158/1055-9965.EPI-13-0562

    Article  CAS  Google Scholar 

  22. Mc Menamin ÚC, Murray LJ, Hughes CM, Cardwell CR (2016) Statin use and breast cancer survival: a nationwide cohort study in Scotland. BMC Cancer 16:600. https://doi.org/10.1186/s12885-016-2651-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nickels S, Vrieling A, Seibold P et al (2013) Mortality and recurrence risk in relation to the use of lipid-lowering drugs in a prospective breast cancer patient cohort. PLoS ONE 8:e75088. https://doi.org/10.1371/journal.pone.0075088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liu B, Yi Z, Guan X et al (2017) The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis. Breast Cancer Res Treat 164:1–11. https://doi.org/10.1007/s10549-017-4246-0

    Article  CAS  PubMed  Google Scholar 

  25. Mansourian M, Haghjooy-Javanmard S, Eshraghi A et al (2016) Statins use and risk of breast cancer recurrence and death: a systematic review and meta-analysis of observational studies. J Pharm Pharm Sci 19:72–81

    Article  PubMed  Google Scholar 

  26. Manthravadi S, Shrestha A, Madhusudhana S (2016) Impact of statin use on cancer recurrence and mortality in breast cancer: a systematic review and meta-analysis. Int J Cancer 139:1281–1288. https://doi.org/10.1002/ijc.30185

    Article  CAS  PubMed  Google Scholar 

  27. Braithwaite D, Moore DH, Satariano WA et al (2012) Prognostic impact of comorbidity among long-term breast cancer survivors: results from the LACE study. Cancer Epidemiol Biomark Prev 21:1115–1125. https://doi.org/10.1158/1055-9965.EPI-11-1228

    Article  Google Scholar 

  28. Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383

    Article  CAS  PubMed  Google Scholar 

  29. Garwood ER, Kumar AS, Baehner FL et al (2010) Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res Treat 119:137–144. https://doi.org/10.1007/s10549-009-0507-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the patients and families who were included in this study. YRL is supported by the NIH NCI F32 individual post-doctoral fellowship.

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Authors and Affiliations

  1. Department of Endocrine and Oncologic Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, 10th Floor South, Philadelphia, PA, 19104, USA

    Yun Rose Li, Vicky Ro, Laura Steel, Elena Carrigan, Jenny Nguyen, Austin Williams, Alycia So & Julia Tchou

  2. Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, 1600 Divisadero St., Suite H1031, CA, 94143-1708, USA

    Yun Rose Li

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  1. Yun Rose Li
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Contributions

LS, EC, JN, AW, AS, and VR performed data collection. YRL and AW performed data analysis. YRL, VR, and JT wrote the manuscript. All authors have approved the final article.

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Correspondence to Yun Rose Li or Julia Tchou.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Patient healthcare record data used for this setting was retrospective in nature and approved by the University of Pennsylvania Institutional Review Board for Human Subjects Research. All patient health records were maintained in strict confidentiality in compliance with HIPPA requirements, and research conducted was considered to be minimal risk.

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Li, Y.R., Ro, V., Steel, L. et al. Impact of long-term lipid-lowering therapy on clinical outcomes in breast cancer. Breast Cancer Res Treat 176, 669–677 (2019). https://doi.org/10.1007/s10549-019-05267-z

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