Meta-analysis of the effects of beta blocker on survival time in cancer patients

Choi, Chel Hun; Song, Taejong; Kim, Tae Hyun; Choi, Jun Kuk; Park, Jin‐Young; Yoon, Aera; Lee, Yoo-Young; Kim, Tae-Joong; Bae, Duk-Soo; Lee, Jeong‐Won; Kim, Byoung-Gie

doi:10.1007/s00432-014-1658-7

Cited by 72 publications

(51 citation statements)

References 39 publications

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“…The meta‐analysis demonstrated that BB use was associated with prolonged overall survival and disease‐free survival. Further analysis according to cancer type suggested significant effect in breast, ovarian and lung cancer, but not in prostate cancer and melanoma . Our study provides the first clinical evidence demonstrating overall and disease specific survival benefit associated with the use of BB in MM patients.…”

Section: Discussionmentioning

confidence: 61%

Beta‐blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation

et al. 2016

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A preclinical study demonstrated anti‐proliferative and apoptotic effect of propranolol on multiple myeloma (MM) cell. Clinical studies suggested that beta‐blocker (BB) might impact the prognosis of breast, prostate, colorectal, ovarian, lung, and skin cancer. This retrospective study evaluated the effect of BB in MM disease‐specific survival (DSS) and overall survival (OS). Among 1,971 newly diagnosed MM patients seen at Mayo Clinic between 1995 and 2010, usage of BB and other cardiac (or antihypertensive) medications were abstracted. Cumulative incidence function and Kaplan–Meier method were used to estimate 5‐year cumulative incidence rate (CIR) of MM death and OS rate, respectively. Nine hundred and thirty (47.2%) patients had no intake of cardiac medications; 260 (13.2%) used BB alone; 343 (17.4%) used both BB/non‐BB cardiac medications; and 438 (22.2%) had non‐BB cardiac drugs. Superior MM DSS was observed in BB only users, compared to patients without any cardiac drugs ( HRadj.CS, 0.53, 95% confidence interval [CI], 0.42–0.67, P adj.<0.0001) and non‐BB cardiac drugs users ( HRadj.CS, 0.49, 95% CI, 0.38–0.63, P adj.<0.0001). Patients on both BB and other cardiac drugs showed superior DSS than non‐cardiac drugs users ( HRadj.CS, 0.54, 95% CI, 0.44–0.67, P adj.<0.0001) and non‐BB cardiac drug users. ( HRadj.CS, 0.50, 95% CI, 0.40–0.62, P adj.<0.0001). MM DSS did not differ between BB users with and without other cardiac drugs (P adj.=0.90). Multivariable analysis showed the same pattern for OS. In patients with MM, BB intake is associated with a reduced risk of disease‐specific death and overall mortality in comparison to non‐BB or no use of cardiac drugs. Am. J. Hematol. 92:50–55, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 61%

Beta‐blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation

et al. 2016

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“…Innervation of the primary tumor has been shown to promote invasiveness, and examination of adrenergic signaling on primary tumor cells and cell lines has demonstrated increased invasiveness and metastatic potential of these cells (39,40). Further, therapy which suppresses beta-adrenergic receptor signaling has been shown to improve relapse free survival, supporting the role of adrenergic signaling in reactivation of dormant tumor cells (41,42). Moreover, Magnon and co-authors (40) completed a series of studies using mice bearing PC3 prostate tumor xenografts that developed tumors and were monitored for metastases.…”

Section: Discussionmentioning

confidence: 87%

Sympathetic Signaling Reactivates Quiescent Disseminated Prostate Cancer Cells in the Bone Marrow

Decker

Jung

Cackowski

et al. 2017

Molecular Cancer Research

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Clinical observations have identified an association between psychological stress and cancer relapse; suggesting that the sympathetic nervous system/norepinephrine (NE) plays a role in reactivation of dormant disseminated tumor cells (DTCs) in the bone marrow niche. Here, the mechanism by which NE regulates prostate cancer (PCa) DTCs in the marrow is explored. NE directly stimulated PCa cell proliferation through β2-adrenergic receptors (ADRB2). NE also altered PCa proliferation in the marrow niche by indirectly by downregulating the secretion of the dormancy inducing molecule growth arrest specific-6 (GAS6) expressed by osteoblasts. These observations were confirmed in co-cultures of PCa cells expressing the fluorescent ubiquitination-based cell cycle reporters (FUCCI) and osteoblasts isolated from GAS6-deficient (GAS6−/−) animals. A novel ex vivo model system, using femurs harvested from GAS6+/+ or GAS6−/− mice, was used to confirm these results. As in co-culture, when PCa cells were injected into the marrow cavities of GAS6+/+ femurs, NE altered the PCa cell cycle. However, NE had less of an impact on PCa cells in femur explants isolated from GAS6−/− mice. Together, this study demonstrate that NE reactivates PCa cell-cycling through both a direct action on PCa cells and indirectly on adjacent niche cells

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“…This was indeed observed in a small number of retrospective studies. 65 b-blockers are safe and well-characterized drugs, used clinically for the treatment of congestive heart failure and high blood pressure. Although these drugs do not seem to affect breast cancer incidence and tumorigenesis, a beneficial effect in terms of less advanced disease at diagnosis and lower cancer-specific mortality was observed in patients who have taken propranolol 1 year before diagnosis.…”

Section: Stress B-blockers and Survival In Patients With Breast Cancermentioning

confidence: 99%

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

Elefteriou¹

2015

BoneKEy Reports

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Improved detection programs and new therapies significantly improved the 5-year survival rate of women with breast cancer. However, some women still relapse and succumb to cancer because of metastatic disease. In particular, chronically depressed patients do not seem to benefit from newly developed treatments and present with shorter survival. The reason for this association is unclear, but recent cues from preclinical studies point to the possible contribution of neuroendocrine factors generated in response to chronic stress and depression. Retrospective clinical studies also suggest a beneficial effect of sympathetic blockade in terms of less advanced disease at diagnosis, lower cancer-specific mortality, longer disease-free survival and reduced metastasis development and tumor recurrence, especially in patients who have taken propranolol before diagnosis. Therefore, b-blockers or therapies normalizing sympathetic tone might be beneficial as early adjuvant therapies to limit skeletal metastases and growth and eventually to improve prognosis in patients with breast cancers.

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Meta-analysis of the effects of beta blocker on survival time in cancer patients

Abstract: This meta-analysis provides evidence that beta blocker use can be associated with the prolonged survival of cancer patients, especially patients with early-stage cancer treated primarily with surgery.

Cited by 72 publications

References 39 publications

Beta‐blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation

Beta‐blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation

Sympathetic Signaling Reactivates Quiescent Disseminated Prostate Cancer Cells in the Bone Marrow

Chronic stress, sympathetic activation and skeletal metastasis of breast cancer cells

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