β-Blocker Use and Risk of Recurrence in Patients with Early Breast Cancer

Sakellakis, Minas; Kostaki, Anastasia; Starakis, Ioannis; Koutras, Angelos

doi:10.1159/000371871

Cited by 21 publications

(28 citation statements)

References 3 publications

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“…Our results are in line with preclinical in vitro and in vivo studies, showing the antiangiogenetic and antimetastatic property of BB, in particular propranolol . Beside preclinical studies, a significant reduction in BC specific mortality and recurrence was observed in some previous observational studies, while others did not confirm these results …”

Section: Discussionsupporting

confidence: 88%

Use of beta‐blockers, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta‐analysis

Raimondi

Botteri

Munzone

et al. 2016

Intl Journal of Cancer

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Breast cancer (BC) is the second leading cause of cancer death among women in Western Countries. Beta-blocker (BB) drugs, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were suggested to have a favorable role in the development and progression of BC. We have performed a meta-analysis to clarify the potential benefits of these drugs on BC survival. A total number of 46 265 BC patients from eleven papers were included, ten independent studies on BB use and seven on ACEi/ARB use. The summary hazard ratio (SHR) was estimated by pooling the study-specific estimates with random effects models and maximum likelihood estimation. We assessed the homogeneity of the effects across studies and evaluated between-study heterogeneity by meta-regression and sensitivity analyses. We found a significant improvement in BC specific survival for patients treated with BB drugs at the time of BC diagnosis (SHR: 0.44; 95%CI: 0.26-0.73 with I 2 5 78%). We also observed a borderline significant improvement in disease free survival for subjects treated with BB (SHR: 0.71, 95%CI: 0.19-1.03). No association of ACEi/ARB use with disease free and overall survival was found. In conclusion, we report epidemiological evidence that BB improve BC-specific survival. Clinical trials addressing this hypothesis are warranted.Breast cancer (BC) is the second most common newly diagnosed cancer and second leading cause of cancer death among women in the US and the other western countries. Death rates from BC have been declining since about 1989, with larger decreases in women younger than 50 years. These decreases are believed to be the result of earlier detection through screening and increased awareness, as well as improved treatment.1 However, despite the use of modern adjuvant treatments, a significant proportion of BC patients still develop recurrent disease and distant metastasis. The biological aggressiveness of cancers, as well as the metastatic potential may be influenced by a wide range of host-related factors, 2 including age, menopausal status, 3 obesity, diabetes, insulin resistance, hypertension 4-7 as well as physical activity and alcohol consumption. 8,9 Recently, increasing attention has been put toward comorbid conditions and their associated medications as potential factors influencing BC progression, recurrence and mortality. 6,10,11 Beta-blocker (BB) drugs [adrenergic receptor (AR) antagonists also known as beta-adrenoceptor blocking agents] are clinically well characterized for the treatment of hypertension and were proven effective in reducing life-threatening cerebrovascular events.12 Recent studies [13][14][15][16] suggested that BB have a role in reducing tumor metastasis, tumor recurrence and cancer-specific mortality.These hypotheses are based on several preclinical models suggesting a possible role of stress as a factor influencing inflammatory processes in the tumor microenvironment. The catecholamine stress hormone norepinephrine induces tumor cell migration and metastasis, working t...

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Section: Discussionsupporting

confidence: 88%

Use of beta‐blockers, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta‐analysis

Raimondi

Botteri

Munzone

et al. 2016

Intl Journal of Cancer

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“…No significant association was found between β-blocker use and mortality of breast cancer patients in six studies (Ganz et al, 2011;Sendur et al, 2012;Cardwell et al, 2013;Holmes et al, 2013aHolmes et al, , 2013bSakellakis et al, 2015), two of which, nevertheless, reported a nonstatistically significant decreased risk of breast cancer death (Ganz et al, 2011;Holmes et al, 2013a). Melhem-Bertrandt et al (2011) showed that overall survival of breast cancer patients was not affected by β blockers, but relapse-free survival was significantly improved, especially in triple-negative breast cancer patients.…”

Section: Discussionmentioning

confidence: 97%

“…Ten studies have investigated the effect of β-blocker use on the survival of breast cancer patients (Powe et al, 2010;Barron et al, 2011;Ganz et al, 2011;Melhem-Bertrandt et al, 2011;Sendur et al, 2012;Botteri et al, 2013;Cardwell et al, 2013;Holmes et al, 2013aHolmes et al, , 2013bSakellakis et al, 2015). No significant association was found between β-blocker use and mortality of breast cancer patients in six studies (Ganz et al, 2011;Sendur et al, 2012;Cardwell et al, 2013;Holmes et al, 2013aHolmes et al, , 2013bSakellakis et al, 2015), two of which, nevertheless, reported a nonstatistically significant decreased risk of breast cancer death (Ganz et al, 2011;Holmes et al, 2013a).…”

Section: Discussionmentioning

confidence: 99%

“…A number of epidemiologic studies have attempted to link the use of β blockers to mortality in patients with several cancer types including melanoma (Lemeshow et al, 2011;Livingstone et al, 2013;De Giorgi et al, 2014;McCourt et al, 2014;Moser et al, 2014), breast (Powe et al, 2010;Barron et al, 2011;Ganz et al, 2011;Melhem-Bertrandt et al, 2011;Sendur et al, 2012;Botteri et al, 2013;Cardwell et al, 2013;Holmes et al, 2013aHolmes et al, , 2013bSakellakis et al, 2015), colorectal (Engineer et al, 2013;Hicks et al, 2013;Holmes et al, 2013b;Jansen et al, 2014), prostate (Grytli et al, 2013(Grytli et al, , 2014Holmes et al, 2013b;Assayag et al, 2014;Cardwell et al, 2014), ovarian (Diaz et al, 2012;Johannesdottir et al, 2013), and lung cancer (Wilop et al, 2009;Aydiner et al, 2013;Wang et al, 2013;Holmes et al, 2013b;Cata et al, 2014); some have indicated that β-blocker use was associated with longer survival, whereas others showed no effect or a harmful effect. To date, no meta-analysis has investigated the impact of β-blocker use on the survival of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies

Zhong

Yu²,

Zhang³

et al. 2016

European Journal of Cancer Prevention

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A number of epidemiologic studies have attempted to link the use of β blockers to mortality in cancer patients, but their findings have been inconclusive. A meta-analysis was carried out to derive a more precise estimation. Relevant studies were identified by searching PubMed and EMBASE to May 2015. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. Twenty cohort studies and four case-control studies involving 76 538 participants were included. The overall results showed that patients who used β blockers after diagnosis had an HR of 0.89 (95% CI 0.81-0.98) for all-cause mortality compared with nonusers. Those who used β blockers after diagnosis (vs. nonusers) had an HR of 0.89 (95% CI 0.79-0.99) for cancer-specific mortality. Prediagnostic use of β blockers showed no beneficial effect on all-cause mortality or cancer-specific mortality. Stratifying by cancer type, only breast cancer patients who used β blockers after diagnosis had a prolonged overall survival. A linear but nonsignificant trend was found between postdiagnostic β-blocker use and mortality of cancer patients. In conclusion, the average effect of β-blocker use after diagnosis but not before diagnosis is beneficial for the survival of cancer patients.

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“…We chose to evaluate β-blockers (BB) since previous studies evaluated the effect of BB on mortality in cancer patients in general and in breast cancer patients specifically, but their findings were inconclusive [23,26,27,28,29,30]. …”

Section: Methodsmentioning

confidence: 99%

The Association between Angiotensin Receptor Blocker Usage and Breast Cancer Characteristics

Goldvaser¹,

Rizel²,

Hendler³

et al. 2016

Oncology

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Purpose: To evaluate the association between angiotensin receptor blocker (ARB) usage and breast cancer characteristics and outcomes. Methods: All patients who were treated in our institute for estrogen receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer between April 2005 and March 2012 and whose tumors were sent for Oncotype-DX analysis were included. Medical records were retrospectively reviewed. Data regarding ARB usage were retrieved. Usage of several prespecified medications for hypertension was also evaluated. Each medication group was compared with the rest of the cohort. Results: A total of 671 patients were included. Forty-six (7%) patients were treated with ARB. ARB usage was associated with macroscopic nodal involvement (p < 0.001) and a more advanced stage at diagnosis (p < 0.001). These findings remained significant in the multivariate analysis. Patients treated with ARB also had a higher incidence of invasive lobular carcinoma subtype (p = 0.009), a worse 5-year breast cancer-specific survival (94.7 vs. 98.8%, p = 0.024) and a worse 5-year overall survival (94.6 vs. 98.8%, p = 0.015), but these differences were not demonstrated in the multivariate analysis. Conclusions: Patients treated with ARB presented with a more advanced breast cancer disease and some distinct histological features. Further research is required to elucidate the effect of ARB treatment on breast cancer.

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β-Blocker Use and Risk of Recurrence in Patients with Early Breast Cancer

Cited by 21 publications

References 3 publications

Use of beta‐blockers, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta‐analysis

Use of beta‐blockers, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta‐analysis

β-Blocker use and mortality in cancer patients: systematic review and meta-analysis of observational studies

The Association between Angiotensin Receptor Blocker Usage and Breast Cancer Characteristics

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