Can all beta blockers improve the breast cancer survival?

Abstract

Recent studies have showed the importance of neuroendocrine regulation of breast cancer progression. Preclinical and epidemiological studies have designated that sympathetic nervous system and adrenergic neurotransmitters such as epinephrine and neuroepinephrine can regulate several pathways for tumor progression and metastasis.1Entschladen F. Drell TLt Lang K. Joseph J. Zaenker K.S. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters.Lancet Oncol. 2004; 5: 254-258Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar Emerging data suggest a dramatic new role for β-blockers in the treatment of breast cancer. However, there is limited data about the association of breast cancer and with a selective metoprolol usage. Thus, we aimed to investigate relationship between metoprolol usage and clinico-pathological properties of breast cancer. Between 1998 and 2010 years 1978 patients with breast cancer was admitted to our clinic. Breast cancer patients who were taking oral metoprolol more than 12 months were enrolled as a metoprolol users (n = 88), where the patients matched with the same age who were not taking oral metoprolol were included as a control group (n = 456). Median age of both metoprolol users and nonusers was 55 (30–83). The mean duration of metoprolol usage was 26 ± 13.2 months. Baseline tumor characteristics of the participants are described in Table 1. There were no apparent differences in terms of baseline tumor size, grade, axillary lymph node involvement and hormonal receptor status between metoprolol users and nonusers. Furthermore, there were no differences in overall survival and disease free survival (DFS) in both groups. In patients with metoprolol users DFS rate was 98.3% whereas 90.4% in nonusers in third years (P = 0.13). Five year survival rate in metoprolol users was 96.8%, whereas in nonusers was 92.9% (P = 0.28).Table 1Baseline tumor characteristics according to metoprolol use.CharacteristicMetoprolol useYes (n = 88)No (n = 456)P-valuen (%)n (%)Total88456Estrogen receptor Positive40 (83.3)309 (73.2)0.23 Negative8 (16.7)113 (26.8)Progesterone receptor Positive39 (81.3)306 (72.3)0.22 Negative9 (18.7)117 (27.7)HER2 Positive12 (22.2)93 (21.5)0.38 Negative32 (77.8)338 (78.5)Triple negative Yes4 (9.5)48 (11.4)0.40 No38 (90.5)372 (88.6)Lenfovascular invasion No65 (77.3)292 (71.1)0.19 Yes19 (22.7)119 (28.9)Grade I14 (18.9)45 (10.9)0.08 II38 (51.4)186 (45.1) III22 (29.7)181 (43.9)T-Stage T126 (31.7)115 (26.6)0.40 T241 (50.0)235 (54.4) T310 (12.2)60 (13.9) T45 (6.1)22 (5.1)Lymph node status Node (−)41 (50)192 (44.5)0.13 Node (+)41(50)232 (55.5)Distant metastasis No74 (85.1)417 (91.5)0.07 Yes13 (14.9)39 (8.5)Abbreviations: HER, Hercept test for Her2/Neu. Open table in a new tab Abbreviations: HER, Hercept test for Her2/Neu. Metoprolol is one of the most common beta blocker widely used in the treatment of hypertension and cardiovascular disease. Metoprolol is highly selective β1-receptor blocker.2Packer M. Beta-blockade in heart failure. Basic concepts and clinical results.Am J Hypertens. 1998; 11: 23S-37SCrossref PubMed Scopus (36) Google Scholar Melhem-Bertrandt et. al reported that adding beta blockers to neoadjuvant chemotherapy had increased the relapse free survival in triple negative breast cancer patients.3Melhem-Bertrandt A. Chavez-Macgregor M. Lei X. Brown E.N. Lee R.T. Meric-Bernstam F. et al.Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer.J Clin Oncol. 2011; 29: 2645-2652Crossref PubMed Scopus (332) Google Scholar Baron et al had reported that especially β2-adrenergic signaling pathway can reduce breast cancer progression and mortality. In this study, women taking propranolol (β1 and β2 antagonist) before breast cancer diagnosis were significantly better pathological properties and lower breast cancer specific mortality compared to nonusers whereas there was no differences in pathological properties and breast cancer specific mortality between atenolol (β1 antagonist) users and nonusers.4Barron T.I. Connolly R.M. Sharp L. Bennett K. Visvanathan K. Beta blockers and breast cancer mortality: a population - based study.J Clin Oncol. 2011; 29: 2635-2644Crossref PubMed Scopus (393) Google Scholar In another study Shah et. al showed that both selective and non-selective beta blockers did not improve survival in cancer patients.5Shah S.M. Carey I.M. Owen C.G. Harris T. Dewilde S. Cook D.G. Does beta-adrenoceptor blocker therapy improve cancer survival? Findings from a population-based retrospective cohort study.Br J Clin Pharmacol. 2011; 72: 157-161Crossref PubMed Scopus (103) Google Scholar In a recently published study both selective and non-selective beta blockers was associated with a significant reduction in the formation of distant metastases and a reduced risk of breast cancer–related mortality.6Powe D.G. Voss M.J. Zanker K.S. Habashy H.O. Green A.R. Ellis I.O. et al.Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.Oncotarget. 2010; 1: 628-638Crossref PubMed Scopus (364) Google Scholar Our observations showed no difference in pathological and survival properties between β1-selective blocker metoprolol users and nonusers. Because of these contradictory results of beta blockers on pathological properties and survival functions, further studies in larger cohorts are needed. The authors indicated no potential conflicts of interest.