J Clin Oncol. 2011 May 31. [Epub ahead of print]
Beta Blockers and Breast Cancer Mortality: A Population-Based Study.
Barron TI,
Connolly RM,
Sharp L,
Bennett K,
Visvanathan K.
LINK
Source
Trinity College, University of Dublin, Dublin; National Cancer Registry Ireland, Cork, Ireland; and Johns Hopkins School of Medicine, Sidney Kimmel Comprehensive Cancer Centre; Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
Abstract
PURPOSE Preclinical studies have demonstrated that antagonism of β(2)-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer-specific mortality. PATIENTS AND METHODS Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β(1)/β(2) antagonist; n = 70) or atenolol (β(1) antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer-specific mortality were assessed. Results Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer-specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer-specific mortality between atenolol users and matched nonusers. CONCLUSION The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β(2)-adrenergic signaling pathway can reduce breast cancer progression and mortality.
- PMID:
- 21632503
- [PubMed - as supplied by publisher]
In contrast:
Br J Clin Pharmacol. 2011 Jul;72(1):157-61. doi: 10.1111/j.1365-2125.2011.03980.x.
Does β-adrenoceptor blocker therapy improve cancer survival? Findings from a population-based retrospective cohort study.
Shah SM,
Carey IM,
Owen CG,
Harris T,
Dewilde S,
Cook DG.
LINK
Source
Division of Population Health Sciences and Education, St George's University of London, Tooting, London SW17 0RE, UK.
Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In vitro studies suggest that β-adrenoceptor blocker therapy inhibits cancer cell proliferation and migration leading to their consideration as novel therapeutic agents for cancer. • While trials in humans have suggested β-adrenoceptor blockers have no effect on cancer incidence, their effect on cancer survival has not been studied. • Recent limited evidence in breast cancer patients suggests that β-adrenoceptor blockers may improve cancer-specific survival. WHAT THIS STUDY ADDS • This study is the first to examine cancer survival in patients receiving β-adrenoceptor blockers across a range of common cancers in a large population-based sample. • For common tumour sites, including lung, breast and colon, there was no evidence that β-adrenoceptor blocker treatment modified overall survival but poorer survival was seen in patients with prostate and pancreatic cancer. • Our findings do not support development of clinical trials on β-adrenoceptor blocker therapy for cancer without further evidence of a beneficial effect in humans. AIMS To examine the effect of β-adrenoceptor blocker treatment on cancer survival. METHODS In a UK primary care database, we compared patients with a new cancer diagnosis receiving β-adrenoceptor blockers regularly (n= 1406) with patients receiving other antihypertensive medication (n= 2056). RESULTS Compared with cancer patients receiving other antihypertensive medication, patients receiving β-adrenoceptor blocker therapy experienced slightly poorer survival (HR = 1.18, 95% CI 1.04, 1.33 for all β-adrenoceptor blockers; HR = 1.21, 95% CI 0.94, 1.55 for non-selective β-adrenoceptor blockers). This poorer overall survival was explained by patients with pancreatic and prostate cancer with no evidence of an effect on survival for patients with lung, breast or colorectal cancer. Analysis in a cancer-free matched parallel cohort did not suggest selection bias masked a beneficial effect. CONCLUSION Our study does not support the hypothesis that β-adrenoceptor blockers improve survival for common cancers.
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
- PMID:
- 21453301
- [PubMed - in process]
J Clin Oncol. 2011 May 31. [Epub ahead of print]
Expanding Our Therapeutic Options: Beta Blockers for Breast Cancer?
Ganz PA,
Cole SW.
LINK
Source
University of California, Los Angeles (UCLA) School of Public Health; Jonsson Comprehensive Cancer Center at UCLA; David Geffen School of Medicine at UCLA, Los Angeles, CA.
- PMID:
- 21632500
- [PubMed - as supplied by publisher]
Oncotarget. 2010 Nov;1(7):628-38.
Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.
Powe DG,
Voss MJ,
Zänker KS,
Habashy HO,
Green AR,
Ellis IO,
Entschladen F.
Source
Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK.
des.powe@nottingham.ac.uk
Abstract
Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.
Comment in
Pharmacol Ther. 2011 May;130(2):177-90. Epub 2011 Jan 26.
Common cardiovascular medications in cancer therapeutics.
Vaklavas C,
Chatzizisis YS,
Tsimberidou AM.
LINK
Source
Phase 1 Program, Department of Investigational Cancer Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Abstract
Cardiac glycosides, statins, β-blockers, angiotensin-I converting enzyme inhibitors (ACEIs), and angiotensin II type 1 receptor blockers (ARBs) are widely used cardiovascular medications with pleiotropic properties. Many of these medications have been investigated in other diseases, including cancer. Cardiac glycosides and statins have advanced to clinical trial testing in cancer therapeutics, with variable success. Early observations in breast cancer were consistent with a more benign histologic phenotype among women taking digitalis compared to their counterparts who did not receive cardiac glycosides. Cardiac glycosides can induce apoptosis in cancer cells through various mechanisms and sensitize them to the effects of antitumor therapy. By blocking the generation of prenyl units, statins impair prenylation, an important posttranslational modification of proteins whose function depends on membrane anchoring. Statins also impair protein folding and N-glycosylation and inhibit the upregulation of cholesterol synthesis associated with chemotherapy resistance. Stress and catecholamine release promote tumor growth and angiogenesis, effects that can be mitigated by β-blockers. Components of the renin-angiotensin-aldosterone system are expressed in various cancers and are involved in carcinogenesis and tumor progression. Angiotensin II has potent mitogenic and angiogenic properties that can be blocked with ACEIs and ARBs. Although it is unclear whether the promising preclinical activity of many cardiovascular medications has clinically meaningful implications beyond the benefit in cardiovascular morbidity and mortality, the prevention or improvement of prognosis of common malignancies with medications known to reduce cardiovascular morbidity and mortality is encouraging and deserves further clinical investigation.
Copyright © 2011 Elsevier Inc. All rights reserved.
- PMID:
- 21277894
- [PubMed - in process]
Oncotarget. 2010 Nov;1(7):628-38.
Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival.
Powe DG,
Voss MJ,
Zänker KS,
Habashy HO,
Green AR,
Ellis IO,
Entschladen F.
Source
Department of Cellular Pathology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, UK.
des.powe@nottingham.ac.uk
Abstract
Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a non-hypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. Kaplan-Meier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.
Comment in
J Clin Oncol. 2011 May 31. [Epub ahead of print]
Beta-Blocker Use Is Associated With Improved Relapse-Free Survival in Patients With Triple-Negative Breast Cancer.
Melhem-Bertrandt A,
Chavez-Macgregor M,
Lei X,
Brown EN,
Lee RT,
Meric-Bernstam F,
Sood AK,
Conzen SD,
Hortobagyi GN,
Gonzalez-Angulo AM.
LINK
Source
Amal Melhem-Bertrandt, Mariana Chavez-MacGregor, Xiudong Lei, Erika N. Brown, Richard T. Lee, Funda Meric-Bernstam, Anil K. Sood, Gabriel N. Hortobagyi, Ana-Maria Gonzalez-Angulo, The University of Texas MD Anderson Cancer Center, Houston, TX; and Suzanne D. Conzen, the University of Chicago, Chicago, IL.
Abstract
PURPOSE To examine the association between beta-blocker (BB) intake, pathologic complete response (pCR) rates, and survival outcomes in patients with breast cancer treated with neoadjuvant chemotherapy. PATIENTS AND METHODS We retrospectively reviewed
1,413 patients with breast cancer who received neoadjuvant chemotherapy between 1995 and 2007. Patients taking BBs at the start of neoadjuvant therapy were compared with patients with no BB intake. Rates of pCR between the groups were compared using a χ(2) test. Cox proportional hazards models were fitted to determine the association between BB intake, relapse-free survival (RFS), and overall survival (OS). Results Patients who used BBs (n = 102) were compared with patients (n = 1,311) who did not. Patients receiving BBs tended to be older and obese (P < .001). The proportion of pCR was not significantly different between the groups (P = .48).
After adjustment for age, race, stage, grade, receptor status, lymphovascular invasion, body mass index, diabetes, hypertension, and angiotensin-converting enzyme inhibitor use, BB intake was associated with a significantly better RFS (hazard ratio [HR], 0.52; 95% CI, 0.31 to 0.88) but not OS (P = .09). Among patients with triple-negative breast cancer (TNBC; n = 377), BB intake was associated with improved RFS (HR, 0.30; 95% CI, 0.10 to 0.87; P = .027) but not OS (HR, 0.35; 95% CI, 0.12 to 1.00; P = .05). CONCLUSION In this study, BB intake was associated with improved RFS in all patients with breast cancer and in patients with TNBC. Additional studies evaluating the potential benefits of beta-adrenergic blockade on breast cancer recurrence with a focus on TNBC are warranted.
- PMID:
- 21632501
- [PubMed - as supplied by publisher]
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