Verification of the effects of calcium channel blockers on the immune microenvironment of breast cancer

Takada, Koji; Kashiwagi, Shinichiro; Asano, Yuka; Goto, Wataru; Takahashi, Katsuyuki; Fujita, Hisakazu; Takashima, Tsutomu; Tomita, Shuhei; Hirakawa, Kosei; Ohira, Masaichi

doi:10.1186/s12885-019-5828-5

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…A total of 842 potentially eligible studies were retrieved from the selected databases during the initial search. After removing duplicates and further screening the titles and abstracts, 26 studies on breast cancer risk ( Meier et al, 2000 ; Li et al, 2003 ; Gonzalez-Perez et al, 2004 ; Fryzek et al, 2006 ; Largent et al, 2006 ; Davis and Mirick, 2007 ; Van Der Knaap et al, 2008 ; Coogan et al, 2009 ; Largent et al, 2010 ; Huang et al, 2011 ; Hallas et al, 2012 ; Lee et al, 2012 ; Mackenzie et al, 2012 ; Biggar et al, 2013 ; Li et al, 2013 ; Saltzman et al, 2013 ; Devore et al, 2015 ; Numbere et al, 2015 ; Azoulay et al, 2016 ; Chang et al, 2016 ; Gomez-Acebo et al, 2016 ; Wilson et al, 2016 ; Brasky et al, 2017 ; Raebel et al, 2017 ; Busby et al, 2018b ; Zheng et al, 2021 ), and 30 studies on breast cancer prognosis ( Powe et al, 2010 ; Barron et al, 2011 ; Ganz et al, 2011 ; Melhem-Bertrandt et al, 2011 ; Shah et al, 2011 ; Şendur et al, 2012 ; Holmes et al, 2013a ; Holmes et al, 2013b ; Botteri et al, 2013 ; Cardwell et al, 2013 ; Chae et al, 2013 ; Sorensen et al, 2013 ; Boudreau et al, 2014 ; Cardwell et al, 2014 ; Sakellakis et al, 2014 ; Babacan et al, 2015 ; Chen et al, 2015 ; Springate et al, 2015 ; Cardwell et al, 2016 ; Choy et al, 2016 ; Chen et al, 2017 ; Spera et al, 2017 ; Busby et al, 2018a ; Musselman et al, 2018 ; Cui et al, 2019 ; Takada et al, 2019 ; Modi et al, 2...…”

Section: Resultsmentioning

confidence: 99%

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis

Xie

Men

et al. 2021

Front. Pharmacol.

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Background: The prevalence rate of hypertension and breast cancer increases with advancing age. Renin-angiotensin system inhibitors (RASIs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics are widely used to treat patients with hypertension. Although, the association between the use of antihypertensive medication and breast cancer has been highly debated, recent evidence supporting this association remains controversial.Objective: To evaluate the association between the use of antihypertensive medication and the risk of breast cancer and its prognosis.Methods: This study was conducted using data from the PubMed, Embase, and Cochrane Library databases retrieved for the period from January 2000 to April 2021. Articles and their references were checked and summary effects were calculated using random- and fixed-effects models. Heterogeneity test and sensitivity analysis were also performed.Results: This meta-analysis included 57 articles, which were all related to breast cancer risk or prognosis. Assessment of breast cancer risk using the pooled data showed that the use of BBs or CCBs or diuretics was associated with increased cancer risk [BB: relative risk (RR) = 1.20, 95% confidence interval (CI) = 1.09–1.32; CCBs: RR = 1.06, 95% CI 1.03–1.08; diuretics: RR = 1.06, 95% CI 1.01–1.11]. Long-term use of diuretic increased the risk of breast cancer (RR = 1.10, 95% CI 1.01–1.20), whereas long-term RASIs treatment reduced the risk (RR = 0.78, 95% CI 0.68–0.91). In addition, we found that diuretic users may be related to elevated breast cancer-specific mortality [hazard ratio (HR) = 1.18, 95% CI 1.04–1.33], whereas using other antihypertensive medications was not associated with this prognosis in patients with breast cancer.Conclusion: Using CCBs, BBs, and diuretics increased the risk of breast cancer. In addition, diuretics may elevate the risk of breast cancer-specific mortality. The long-term use of RASIs was associated with a significantly lower breast cancer risk, compared with non-users. Thus, this analysis provides evidence to support the benefits of the routine use of RASIs in patients with hypertension, which has important public health implications.

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Section: Resultsmentioning

confidence: 99%

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis

Xie

Men

et al. 2021

Front. Pharmacol.

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“…Several studies have explored the impact of CCBs on survival in cancer patients. For instance, a small study by Takada et al from 2019 observed that CCBs did not alter prognosis in patients with breast cancer; however, the time of exposure to CCBs was not taken into account (160). Another study from the United Kingdom that included more than 20,000 women with breast cancer reported no change in mortality after adjustment for other covariates (161).…”

Section: Evidence From Clinical Studiesmentioning

confidence: 99%

The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer

et al. 2021

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Cancer is a complex group of diseases that constitute the second largest cause of mortality worldwide. The development of new drugs for treating this disease is a long and costly process, from the discovery of the molecule through testing in phase III clinical trials, a process during which most candidate molecules fail. The use of drugs currently employed for the management of other diseases (drug repurposing) represents an alternative for developing new medical treatments. Repurposing existing drugs is, in principle, cheaper and faster than developing new drugs. Antihypertensive drugs, primarily belonging to the pharmacological categories of angiotensin-converting enzyme inhibitors, angiotensin II receptors, direct aldosterone antagonists, β-blockers and calcium channel blockers, are commonly prescribed and have well-known safety profiles. Additionally, some of these drugs have exhibited pharmacological properties useful for the treatment of cancer, rendering them candidates for drug repurposing. In this review, we examine the preclinical and clinical evidence for utilizing antihypertensive agents in the treatment of cancer.

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“…Another report showed that CCBs inhibit the function of T cells and macrophages (76). Moreover, the immunosuppressive effect of CCBs not only affects lymphocytes in the blood but also lymphocytes in the immune microenvironment (77). Therefore, the use of CCBs is not beneficial for patients with breast cancer complicated with hypertension, which contradicts the recommendation of the guidelines, and more clinical data are needed for further verification.…”

Section: Bbsmentioning

confidence: 99%

A narrative review on the interaction between genes and the treatment of hypertension and breast cancer

Wang¹,

He²,

Zhang³

et al. 2021

Ann Transl Med

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The aim to discuss the close relationship between the common biological mechanisms of breast cancer and hypertension, inflammation and oxidative stress, breast cancer gene mutations breast cancer susceptibility gene (BRCA), G protein-coupled receptor kinase (GRK4), etc. and breast cancer treatment includes chemotherapy, Endocrine therapy, Targeted therapy and anti-angiogenesis drugs. In antiangiogenesis drugs focusing on the mechanism of tyrosine kinase inhibitors (TKI) that may activate the rhoa/ rock pathway to cause hypertension, as well as the relationship between breast cancer and antihypertensive drugs includes angiotensin-converting enzyme inhibitors (ACEIs), Calcium channel blockers (CCBs) and β-blockers (BBs)will be explored.Background: Cardiovascular diseases (CVD) and tumors are the two major types of diseases with the highest mortality rates, while hypertension accounts for the largest proportion of CVDs. A large number of the same or similar risk factors are shared between hypertension and tumors, and they influence each other.Many patients, particularly elderly patients, often present with the coexistence of the two diseases. As medical advances have enabled clinicians to cure tumors, many patients with cancer live longer, leading to a gradual increase in the incidence of CVDs, including hypertension. With the second highest incidence among tumors, breast cancer has gradually attracted widespread attention and has been the topic of numerous studies. Studies have confirmed that CVD is one of the causes of death in elderly patients with breast cancer.Methods: Publications from 1985 to 2020 were retrieved from the Web Of Science, Cochrane Library, PubMed, EMBASE and MEDLINE database. We used a mix of MeSH and keywords.Conclusions: Hypertension and cancer may share a common mechanism. The screening and risk assessment of breast cancer in patients with hypertension must be strengthened. Breast cancer cardiology is the interdisciplinary study of oncology and cardiology, and in-depth research in this field may result in long-term improvements in the survival and prognosis of patients with both clinical hypertension and breast cancer.

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Verification of the effects of calcium channel blockers on the immune microenvironment of breast cancer

Cited by 7 publications

References 39 publications

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis

The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer

A narrative review on the interaction between genes and the treatment of hypertension and breast cancer

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