Skip to main content
Top
Published in: Clinical and Translational Oncology 7/2017

01-07-2017 | Research Article

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

Authors: S.-A. Kim, H. Moon, J.-L. Roh, S.-B. Kim, S.-H. Choi, S. Y. Nam, S. Y. Kim

Published in: Clinical and Translational Oncology | Issue 7/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
2.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
3.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
4.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
5.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
6.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
7.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
15.
go back to reference 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 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
16.
go back to reference Darrow DH, Greene AK, Mancini AJ, Nopper AJ. Diagnosis and management of infantile hemangioma. Pediatrics. 2015;136(4):e1060–104.CrossRefPubMed Darrow DH, Greene AK, Mancini AJ, Nopper AJ. Diagnosis and management of infantile hemangioma. Pediatrics. 2015;136(4):e1060–104.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
19.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
27.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
28.
go back to reference Daling JR. Calcium channel blockers and cancer: is an association biologically plausible? Am J Hypertens. 1996;9(7):713–4.CrossRefPubMed Daling JR. Calcium channel blockers and cancer: is an association biologically plausible? Am J Hypertens. 1996;9(7):713–4.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
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
Authors
S.-A. Kim
H. Moon
J.-L. Roh
S.-B. Kim
S.-H. Choi
S. Y. Nam
S. Y. Kim
Publication date
01-07-2017
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 7/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-016-1608-8

Other articles of this Issue 7/2017

Clinical and Translational Oncology 7/2017 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