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Association Use of Bisphosphonates with Risk of Breast Cancer: A Meta-Analysis.

ABSTRACT: Background:Previous studies have investigated the association between the use of bisphosphonates and the development of breast cancer, which presented controversial results. Thus, this meta-analysis was conducted to summarize the current evidence of the association of bisphosphonate use with breast cancer risk. Methods:A comprehensive search was conducted in PubMed, ISI Web of Knowledge, the Cochrane Library, and Embase from inception to March 2019 by two researches, who independently selected trials, retrieved relevant data, and assessed study quality. The summary relative risk (RR) for the use of bisphosphonates on the risks of developing breast cancer was calculated using a random-effect model. Results:The present meta-analysis, which included four case-control studies, involving 55052 breast cancer cases, and seven retrospective cohort studies, involving 14641 breast cancer cases, assessed the effect of bisphosphonates on breast cancer risk. The random-effect model meta-analysis found a reduced risk of breast cancer with exposure to bisphosphonates with pooled RR of 0.87 (95% confidence interval [CI]: 0.80 to 0.94). The short-term use of bisphosphonates (<1 year) did not render significant alteration (RR = 0.92, 95% CI: 0.82 to 1.03), while a significant 26% risk reduction of breast cancer was noted with long-term use (>1 year) (RR = 0.74, 95% CI: 0.62 to 0.90). A protective effect of bisphosphonates was shown in contralateral breast cancer (RR = 0.41, 95% CI: 0.20 to 0.84). In terms of the type of bisphosphonates, a significant inverse relationship was noted for etidronate, with pooled RR of 0.87 (95% CI: 0.80 to 0.96). Conclusion:This meta-analysis suggested that the use of bisphosphonates was associated with reduced risk of breast cancer, including contralateral breast cancer. Compared to other types of bisphosphonates, only etidronate showed a significant inverse relationship. Additionally, the long-term use (>1 year) of bisphosphonates was more significant in lowering breast cancer risk. Further randomized controlled trials are needed to verify this association. This trial is registered with PROSPERO (registration number: CRD42018105024) (registered on 29 August 2018).

SUBMITTER: Peng R

PROVIDER: S-EPMC7568169 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association Use of Bisphosphonates with Risk of Breast Cancer: A Meta-Analysis.

Peng Rui R Liang Xingzhong X Zhang Gang G Yao Yuan Y Chen Zhen Z Pan Xiaojuan X Wang Jinshan J Liu Genglong G

BioMed research international 20201006

<h4>Background</h4>Previous studies have investigated the association between the use of bisphosphonates and the development of breast cancer, which presented controversial results. Thus, this meta-analysis was conducted to summarize the current evidence of the association of bisphosphonate use with breast cancer risk.<h4>Methods</h4>A comprehensive search was conducted in PubMed, ISI Web of Knowledge, the Cochrane Library, and Embase from inception to March 2019 by two researches, who independe ...[more]

PMID: 33102580

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Project description:Background and objectivesSome evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV) events, atrial fibrillation, myocardial infarction (MI), stroke, and CV death in adults with or at risk for low bone mass.MethodsA systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs) and 95% confidence intervals (CIs) of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.ResultsAbsolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%), atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%), MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%), stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%), and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0%) with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%), not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%). The CV effects did not vary by subgroups or study quality.ConclusionsBisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

Project description:BackgroundBisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects.MethodsWe systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE.FindingsWe identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies.ConclusionsThis meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.

Project description:BackgroundSeveral observational studies have suggested a protective effect of oral bisphosphonates (BP) on the risk of breast cancer, but no such association has been seen in randomized control trials. The role of oral BP in breast cancer prevention remains unclear.AimTo investigate the association between different levels of BP exposure and breast cancer incidence in a cohort of osteoporotic post-menopausal women.Subjects and methodsThis historical prospective study was conducted using the computerized databases of Maccabi Healthcare Services (MHS) in Israel. Included in the study were osteopenic and osteoporotic women aged 55-75 years who started BP therapy between 1998 and 2012. The subjects were enrolled in MHS for at least 3 years before therapy initiation, and had a minimum follow-up of 5 years in MHS. Women with a previous cancer, and women treated with selective estrogen receptor modulators (SERMs) were excluded. BP exposure was expressed in quintiles of proportion of days covered (PDC) with BP during follow-up period and cancer incidence was ascertained by the Israel National Tumor Registry. Person-years of follow-up began on January 1st, 1998 and ended at the date of cancer diagnosis, death, or December 31st, 2012, whichever occurred first.ResultsA total of 11,717 patients (mean age = 66.87 ± 4.38) were eligible for the analysis. During a total of 130,252 person-years of follow-up, (mean 7.2 years) 173 incident cases of breast cancer were diagnosed. Compared to women with a PDC with BP of 20% or lower, the adjusted hazard ratio for breast cancer were HR = 0.81 (95%CI: 0.48-1.39), HR = 0.82 (95%CI: 0.50-1.33), HR = 0.72 (95%CI:0.45-1.15) and HR = 1.14 (95%CI:0.76-1.70) among women with 20-40%, 40-60%, 60%-80%, and 80% or higher, PDC, respectively.ConclusionIn this study, we did not find a significant association between oral BP therapy for osteoporosis and the risk of breast cancer in postmenopausal women. The discrepancy between our results and the reports of such an association in observational studies might originate from an indication bias.

Project description: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.

Project description:ImportancePatients with schizophrenia are considered to have many risk factors for the development of cancer. However, the incidence of breast cancer in women with schizophrenia compared with the general population remains uncertain.ObjectiveTo perform an updated meta-analysis to evaluate the association between schizophrenia and the risk of breast cancer.Data sourcesA systematic search of the PubMed and EMBASE databases was conducted using the search terms schizophrenia, schizophrenic, psychosis, combined with breast and cancer, tumor, neoplasm, or carcinoma. The final literature search was performed on August 15, 2017.Study selectionCohort studies reporting the standardized incidence ratio (SIR) for the risk of breast cancer in women with schizophrenia compared with the general population.Data extraction and synthesisThe meta-analysis adhered to Meta-analysis of Observational Studies in Epidemiology and the Cochrane Handbook for Systematic Reviews of Interventions. Data extraction was performed independently. A random-effects model was used to pool the results, and a recently proposed prediction interval was calculated to describe the heterogeneity.Main outcomes and measuresThe SIR for the risk of breast cancer in women with schizophrenia compared with the general population or those without schizophrenia.ResultsTwelve cohorts including 125?760 women were included in this meta-analysis. The results of the meta-analysis showed that schizophrenia was associated with a significantly increased risk of breast cancer incidence in women (SIR, 1.31; 95% CI, 1.14-1.50; P?<?.001), with significant heterogeneity (P?<?.001; I2?=?89%). Substantial between-study variance was also suggested by the wide prediction interval (0.81-2.10), which indicated that it is possible that a future study will show a decreased breast cancer risk in women with schizophrenia compared with the general population. The subgroup analysis results showed that the association was not significantly affected by whether breast cancer cases were excluded at baseline or the sample size of the included studies.Conclusions and relevanceThe incidence of breast cancer in women with schizophrenia is higher than that of the general female population. However, significant heterogeneity exists among the included studies. Women with schizophrenia deserve intensive prevention and treatment of breast cancer.

Dataset Information

Association Use of Bisphosphonates with Risk of Breast Cancer: A Meta-Analysis.

Publications

Association Use of Bisphosphonates with Risk of Breast Cancer: A Meta-Analysis.

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