Therapeutics

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case–control study

C. McCourt

Department of Dermatology, Belfast Health and Social Care Trust, Belfast, Northern Ireland

Cancer Epidemiology and Health Services Research Group, Centre for Public Health, Institute of Clinical Sciences-B, Royal Victoria Hospital Site, Queen's University Belfast, Grosvenor Road, Belfast, BT12 6BJ Northern Ireland

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H.G. Coleman,

H.G. Coleman

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L.J. Murray,

L.J. Murray

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M.M. Cantwell,

M.M. Cantwell

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O. Dolan,

O. Dolan

Department of Dermatology, Belfast Health and Social Care Trust, Belfast, Northern Ireland

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D.G. Powe,

D.G. Powe

Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust and The John Van Geest Cancer Centre, Nottingham Trent University, Nottingham, U.K

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C.R. Cardwell,

Corresponding Author

C.R. Cardwell

Correspondence

Christopher Cardwell.

E-mail: [email protected]

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C. McCourt,

C. McCourt

Department of Dermatology, Belfast Health and Social Care Trust, Belfast, Northern Ireland

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H.G. Coleman,

H.G. Coleman

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L.J. Murray,

L.J. Murray

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M.M. Cantwell,

M.M. Cantwell

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O. Dolan,

O. Dolan

Department of Dermatology, Belfast Health and Social Care Trust, Belfast, Northern Ireland

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D.G. Powe,

D.G. Powe

Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust and The John Van Geest Cancer Centre, Nottingham Trent University, Nottingham, U.K

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C.R. Cardwell,

Corresponding Author

C.R. Cardwell

Correspondence

Christopher Cardwell.

E-mail: [email protected]

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First published: 05 March 2014

https://doi.org/10.1111/bjd.12894

Citations: 53

Funding sources This work was supported by a clinician training bursary from Cancer Research U.K. (awarded to C.M.). H.G.C. is supported by a Cancer Research U.K. Population Research Postdoctoral Fellowship. This study is based in part on data from the General Practice Research Database obtained under licence from the U.K. Medicines and Healthcare Regulatory Agency. The interpretation and conclusions contained in study are those of the authors alone.

Conflicts of interest None declared.

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Summary

Background

Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers.

Objectives

To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma.

Methods

Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case–control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing.

Results

Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68–1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56–1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality.

Conclusions

Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

References

1 Cancer Research U.K. Skin cancer incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/skin/incidence/ (last accessed 26 February 2014).
Google Scholar
2Marsden JR, Newton-Bishop JA, Burrows L et al. Revised U.K. guidelines for the management of cutaneous melanoma 2010. Br J Dermatol 2010; 163: 238–56.
10.1111/j.1365-2133.2010.09883.x
CAS PubMed Web of Science® Google Scholar
3Aronow WS. Current role of beta-blockers in the treatment of hypertension. Expert Opin Pharmacother 2010; 11: 2599–607.
10.1517/14656566.2010.482561
CAS PubMed Web of Science® Google Scholar
4Annabi B, Lachambre MP, Plouffe K et al. Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion. Pharmacol Res 2009; 60: 438–45.
10.1016/j.phrs.2009.05.005
CAS PubMed Web of Science® Google Scholar
5Chim H, Armijo BS, Miller E et al. Propranolol induces regression of hemangioma cells through HIF-1α-mediated inhibition of VEGF-A. Ann Surg 2012; 256: 146–56.
10.1097/SLA.0b013e318254ce7a
PubMed Web of Science® Google Scholar
6Greenberger S, Bischoff J. Infantile hemangioma – mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med 2011; 1: a006460.
10.1101/cshperspect.a006460
CAS PubMed Web of Science® Google Scholar
7Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol 2010; 163: 269–74.
10.1111/j.1365-2133.2010.09848.x
CAS PubMed Web of Science® Google Scholar
8Entschladen F, Drell TL 4th, Lang K et al. Neurotransmitters and chemokines regulate tumor cell migration: potential for a new pharmacological approach to inhibit invasion and metastasis development. Curr Pharm Des 2005; 11: 403–11.
10.2174/1381612053382197
CAS PubMed Web of Science® Google Scholar
9Ganz PA, Cole SW. Expanding our therapeutic options: beta blockers for breast cancer? J Clin Oncol 2011; 29: 2612–16.
10.1200/JCO.2011.35.8820
PubMed Web of Science® Google Scholar
10Powe DG, Voss MJ, Zänker KS et al. Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival. Oncotarget 2010; 1: 628–38.
10.18632/oncotarget.197
PubMed Web of Science® Google Scholar
11Sanzo M, Colucci R, Arunachalam M et al. Stress as a possible mechanism in melanoma progression. Dermatol Res Pract 2010; 2010: 483493.
10.1155/2010/483493
CAS PubMed Google Scholar
12Scarparo AC, Sumida DH, Patrão MT et al. Catecholamine effects on human melanoma cells evoked by alpha1-adrenoceptors. Arch Dermatol Res 2004; 296: 112–19.
10.1007/s00403-004-0488-x
CAS PubMed Web of Science® Google Scholar
13Simonetti O, Lucarini G, Brancorsini D et al. Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions. Cancer 2002; 95: 1963–70.
10.1002/cncr.10888
CAS PubMed Web of Science® Google Scholar
14Yang EV, Kim SJ, Donovan EL et al. Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression. Brain Behav Immun 2009; 23: 267–75.
10.1016/j.bbi.2008.10.005
CAS PubMed Web of Science® Google Scholar
15Benish M, Bartal I, Goldfarb Y et al. Perioperative use of beta-blockers and COX-2 inhibitors may improve immune competence and reduce the risk of tumor metastasis. Ann Surg Oncol 2008; 15: 2042–52.
10.1245/s10434-008-9890-5
PubMed Web of Science® Google Scholar
16Glasner A, Avraham R, Rosenne E et al. Improving survival rates in two models of spontaneous postoperative metastasis in mice by combined administration of a beta-adrenergic antagonist and a cyclooxygenase-2 inhibitor. J Immunol 2010; 184: 2449–57.
10.4049/jimmunol.0903301
CAS PubMed Web of Science® Google Scholar
17Lang K, Drell TL 4th, Lindecke A et al. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int J Cancer 2004; 112: 231–8.
10.1002/ijc.20410
CAS PubMed Web of Science® Google Scholar
18Pasquier E, Ciccolini J, Carre M et al. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment. Oncotarget 2011; 2: 797–809.
10.18632/oncotarget.343
PubMed Web of Science® Google Scholar
19Sloan EK, Priceman SJ, Cox BF et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res 2010; 70: 7042–52.
10.1158/0008-5472.CAN-10-0522
CAS PubMed Web of Science® Google Scholar
20Palm D, Lang K, Niggemann B et al. The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers. Int J Cancer 2006; 118: 2744–9.
10.1002/ijc.21723
CAS PubMed Web of Science® Google Scholar
21De Giorgi V, Grazzini M, Gandini S et al. Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med 2011; 171: 779–81.
10.1001/archinternmed.2011.131
PubMed Web of Science® Google Scholar
22Lemeshow S, Sørensen HT, Phillips G et al. β-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev 2011; 20: 2273–9.
10.1158/1055-9965.EPI-11-0249
CAS PubMed Web of Science® Google Scholar
23Jick H, Jick SS, Derby LE. Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. BMJ 1991; 302: 766–8.
10.1136/bmj.302.6779.766
CAS PubMed Web of Science® Google Scholar
24Balch CM, Gershenwald JE, Soong SJ et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27: 6199–206.
10.1200/JCO.2009.23.4799
PubMed Web of Science® Google Scholar
25Fleming ID, ed. AJCC Cancer Staging Manual. Philadelphia, PA: Lippincott-Raven, 1997.
Google Scholar
26Khan NF, Perera R, Harper S, Rose PW. Adaptation and validation of the Charlson Index for Read/OXMIS coded databases. BMC Fam Pract 2010; 11: 1.
10.1186/1471-2296-11-1
PubMed Web of Science® Google Scholar
27 Joint Formulary Committee. Non-steroidal anti-inflammatory drugs. In: British National Formulary: BNF 60 ( J Martin, ed). London: Pharmaceutical Press, 2010; 621–629; chapter 10.1.1.
Google Scholar
28Azoulay L, Yin H, Filion KB et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case–control study. BMJ 2012; 344: e3645.
10.1136/bmj.e3645
PubMed Web of Science® Google Scholar
29Schade R, Andersohn F, Suissa S et al. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med 2007; 356: 29–38.
10.1056/NEJMoa062222
CAS PubMed Web of Science® Google Scholar
30Levesque 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: b5087.
10.1136/bmj.b5087
PubMed Web of Science® Google Scholar
31Etminan M, Samii A. Pharmacoepidemiology I: a review of pharmacoepidemiologic study designs. Pharmacotherapy 2004; 24: 964–9.
10.1592/phco.24.11.964.36143
CAS PubMed Web of Science® Google Scholar
32Essebag V, Platt RW, Abrahamowicz M, Pilote L. Comparison of nested case–control and survival analysis methodologies for analysis of time-dependent exposure. BMC Med Res Methodol 2005; 5: 5.
10.1186/1471-2288-5-5
PubMed Google Scholar
33Fine JP, Gray RJ. A proportional hazards model for the sub-distribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.
10.1080/01621459.1999.10474144
Web of Science® Google Scholar
34Livingstone E, Hollestein LM, van Herk-Sukel MP et al. β-Blocker use and all-cause mortality of melanoma patients: results from a population-based Dutch cohort study. Eur J Cancer 2013; 49: 3863–71.
10.1016/j.ejca.2013.07.141
CAS PubMed Web of Science® Google Scholar
35Sosman JA, Kim KB, Schuchter L et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366: 707–14.
10.1056/NEJMoa1112302
CAS PubMed Web of Science® Google Scholar
36Sarfati D, Blakely T, Pearce N. Measuring cancer survival in populations: relative survival versus cancer-specific survival. Int J Epidemiol 2010; 39: 598–610.
10.1093/ije/dyp392
PubMed Web of Science® Google Scholar

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Volume170, Issue4

April 2014

Pages 930-938

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case–control study

Summary

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Conclusions

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Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case–control study

Summary

Background

Objectives

Methods

Results

Conclusions

References

Citing Literature

References

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