Skip to main content
Log in

Postdiagnostic use of β-blockers and other antihypertensive drugs and the risk of recurrence and mortality in head and neck cancer patients: an observational study of 10,414 person–years of follow-up

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Introduction

Growing evidence indicates that norepinephrine promotes cancer growth and metastasis whereas β-blockers decrease these risks. This study aimed to examine the clinical impact of β-blockers and other hypertensive drugs on disease recurrence and survival in patients with head and neck squamous cell carcinoma (HNSCC).

Materials and methods

This study analyzed a cohort of 1274 consecutive patients who received definitive treatments for previously untreated HNSCC at our tertiary referral center between January 2001 and December 2012. Antihypertensive use was considered positive if patients were on medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilized to determine associations between antihypertensive drugs and recurrence, survival, and second primary cancer (SPC) occurrence.

Results

Hypertension itself was not a significant variable of recurrence and survival and no antihypertensive drug use affected SPC occurrence (all P > 0.1). After controlling for clinical factors, calcium-channel blocker use remained an independent variable for index cancer recurrence, and β-blocker use was significantly associated with poor cancer-specific mortality, competing mortality, and all-cause mortality (all P < 0.05). β-blocker use significantly affected competing and all-cause mortalities in normotensive patients, and calcium-channel blocker use affected index cancer recurrence in normotensive patients (all P < 0.05).

Conclusions

Our data show that β-blocker use is associated with decreased survival and calcium-channel blockers is associated with increased cancer recurrence in patients of HNSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cole SW, Nagaraja AS, Lutgendorf SK, Green PA, Sood AK. Sympathetic nervous system regulation of the tumour microenvironment. Nat Rev Cancer. 2015;15(9):563–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70(18):7042–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kim-Fuchs C, Le CP, Pimentel MA, Shackleford D, Ferrari D, Angst E, et al. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain Behav Immun. 2014;40:40–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Barron TI, Connolly RM, Sharp L, Bennett K, Visvanathan K. Beta blockers and breast cancer mortality: a population-based study. J Clin Oncol. 2011;29(19):2635–44.

    Article  CAS  PubMed  Google Scholar 

  5. Wang HM, Liao ZX, Komaki R, Welsh JW, O’Reilly MS, Chang JY, et al. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Ann Oncol. 2013;24(5):1312–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Watkins JL, Thaker PH, Nick AM, Ramondetta LM, Kumar S, Urbauer DL, et al. Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer. Cancer. 2015;121(19):3444–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shah SM, Carey IM, Owen CG, Harris T, Dewilde S, Cook DG. Does beta-adrenoceptor blocker therapy improve cancer survival? Findings from a population-based retrospective cohort study. Br J Clin Pharmacol. 2011;72(1):157–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hicks BM, Murray LJ, Powe DG, Hughes CM, Cardwell CR. Beta-blocker usage and colorectal cancer mortality: a nested case-control study in the UK Clinical Practice Research Datalink cohort. Ann Oncol. 2013;24(12):3100–6.

    Article  CAS  PubMed  Google Scholar 

  9. Assayag J, Pollak MN, Azoulay L. Post-diagnostic use of beta-blockers and the risk of death in patients with prostate cancer. Eur J Cancer. 2014;50(16):2838–45.

    Article  CAS  PubMed  Google Scholar 

  10. Drell TLt, Joseph J, Lang K, Niggemann B, Zaenker KS, Entschladen F. Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-468 human breast carcinoma cells. Breast Cancer Res Treat. 2003;80(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  11. Lang K, Drell TLt, Lindecke A, Niggemann B, Kaltschmidt C, Zaenker KS, et al. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer. 2004;112(2):231–8.

    Article  CAS  PubMed  Google Scholar 

  12. Chang PY, Huang WY, Lin CL, Huang TC, Wu YY, Chen JH, et al. Propranolol reduces cancer risk: a population-based cohort study. Medicine (Baltimore). 2015;94(27):e1097.

    Article  CAS  Google Scholar 

  13. Lin CS, Lin WS, Lin CL, Kao CH. Carvedilol use is associated with reduced cancer risk: a nationwide population-based cohort study. Int J Cardiol. 2015;184:9–13.

    Article  PubMed  Google Scholar 

  14. Shang ZJ, Liu K, de Liang F. Expression of beta2-adrenergic receptor in oral squamous cell carcinoma. J Oral Pathol Med. 2009;38(4):371–6.

    Article  CAS  PubMed  Google Scholar 

  15. Wolter NE, Wolter JK, Enepekides DJ, Irwin MS. Propranolol as a novel adjunctive treatment for head and neck squamous cell carcinoma. J Otolaryngol Head Neck Surg. 2012;41(5):334–44.

    PubMed  Google Scholar 

  16. Darrow DH, Greene AK, Mancini AJ, Nopper AJ. Diagnosis and management of infantile hemangioma. Pediatrics. 2015;136(4):e1060–104.

    Article  PubMed  Google Scholar 

  17. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  Google Scholar 

  18. Kong M, Hong SE. Tumor regression patterns based on follow-up duration in patients with head and neck squamous cell carcinoma treated with radiotherapy or chemoradiotherapy. Clin Exp Otorhinolaryngol. 2015;8(4):416–21.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Moon SH, Choi JY, Lee HJ, Son YI, Baek CH, Ahn YC, et al. Prognostic value of volume-based positron emission tomography/computed tomography in patients with nasopharyngeal carcinoma treated with concurrent chemoradiotherapy. Clin Exp Otorhinolaryngol. 2015;8(2):142–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Harding JL, Sooriyakumaran M, Anstey KJ, Adams R, Balkau B, Brennan-Olsen S, et al. Hypertension, antihypertensive treatment and cancer incidence and mortality: a pooled collaborative analysis of 12 Australian and New Zealand cohorts. J Hypertens. 2016;34(1):149–55.

    Article  CAS  PubMed  Google Scholar 

  21. Grossman E, Messerli FH, Boyko V, Goldbourt U. Is there an association between hypertension and cancer mortality? Am J Med. 2002;112(6):479–86.

    Article  PubMed  Google Scholar 

  22. Stocks T, Van Hemelrijck M, Manjer J, Bjorge T, Ulmer H, Hallmans G, et al. Blood pressure and risk of cancer incidence and mortality in the Metabolic Syndrome and Cancer Project. Hypertension. 2012;59(4):802–10.

    Article  CAS  PubMed  Google Scholar 

  23. Rosengren A, Himmelmann A, Wilhelmsen L, Branehog I, Wedel H. Hypertension and long-term cancer incidence and mortality among Swedish men. J Hypertens. 1998;16(7):933–40.

    Article  CAS  PubMed  Google Scholar 

  24. Lee SY, Kim MT, Jee SH, Im JS. Does hypertension increase mortality risk from lung cancer? A prospective cohort study on smoking, hypertension and lung cancer risk among Korean men. J Hypertens. 2002;20(4):617–22.

    Article  CAS  PubMed  Google Scholar 

  25. Testa G, Cacciatore F, Della-Morte D, Mazzella F, Mastrobuoni C, Galizia G, et al. Atenolol use is associated with long-term mortality in community-dwelling older adults with hypertension. Geriatr Gerontol Int. 2014;14(1):153–8.

    Article  PubMed  Google Scholar 

  26. Hole DJ, Hawthorne VM, Isles CG, McGhee SM, Robertson JW, Gillis CR, et al. Incidence of and mortality from cancer in hypertensive patients. BMJ. 1993;306(6878):609–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li CI, Daling JR, Tang MT, Haugen KL, Porter PL, Malone KE. Use of antihypertensive medications and breast cancer risk among women aged 55–74 years. JAMA Intern Med. 2013;173(17):1629–37.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Daling JR. Calcium channel blockers and cancer: is an association biologically plausible? Am J Hypertens. 1996;9(7):713–4.

    Article  CAS  PubMed  Google Scholar 

  29. Bangalore S, Kumar S, Kjeldsen SE, Makani H, Grossman E, Wetterslev J, et al. Antihypertensive drugs and risk of cancer: network meta-analyses and trial sequential analyses of 324, 168 participants from randomised trials. Lancet Oncol. 2011;12(1):65–82.

    Article  CAS  PubMed  Google Scholar 

  30. Morris LG, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol. 2011;29(6):739–46.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J.-L. Roh.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Funding

This study was supported by a Grant (No. 2015R1A2A1A15054540) from the Basic Science Research Program through the National Research Foundation of Korea (NRF), Ministry of Science, ICT, and Future Planning and a Grant (No. HI15C2920) from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Ministry of Health & Welfare, Seoul, Republic of Korea (J.L. Roh).

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 20 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, SA., Moon, H., Roh, JL. et al. Postdiagnostic use of β-blockers and other antihypertensive drugs and the risk of recurrence and mortality in head and neck cancer patients: an observational study of 10,414 person–years of follow-up. Clin Transl Oncol 19, 826–833 (2017). https://doi.org/10.1007/s12094-016-1608-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-016-1608-8

Keywords

Navigation