Use of Bisphosphonates and Risk of Breast Cancer

Vestergaard, Peter; Fischer, L; Mele, Marco; Mosekilde, Leif; Christiansen, Peer

doi:10.1007/s00223-011-9463-7

Cited by 38 publications

(46 citation statements)

References 37 publications

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“…Two studies were regarded as having mild selection bias [15, 16]. Two of the studies were considered as having moderate comparability because they were only adjusted for two factors [13, 14].…”

Section: Resultsmentioning

confidence: 99%

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The Carcinogenicity of Alendronate in Patients with Osteoporosis: Evidence from Cohort Studies

et al. 2015

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ContextAlendronate may relate to the incidence of cancers, especially esophageal and colon cancer. But the results are inconsistent in different studies.ObjectiveTo quantify the association between the use of alendronate and the occurrence of different types of cancer.Data SourcesWe searched Embase, Pubmed, CENTRAL, SIGLE and clinicaltrials.gov, up to 2014 June.Study SelectionCohort studies reporting association between alendronate or bisphosphonate therapy including alendronate in patients with osteoporosis and risk of cancer were selected by two authors.Data ExtractionTwo authors independently extracted the data. The Chi-square test and the I-square test were used for testing heterogeneity between studies.Data SynthesisEight cohort studies were included in the meta-analysis. Meta-analysis result manifested that alendronate significantly increased the incidence of lung cancer (HR 1.23, 95%CI 1.03 to 1.47, P value = 0.03), nevertheless, there was no significant difference after we excluded either Lee’s 2012 study (HR 1.17, 95%CI 0.95 to 1.44, P value = 0.13) or Chiang’s 2012 study (HR 1.47, 95%CI 1 to 2.17, P value = 0.05). For the incidence of colorectal cancer, no significant difference occurred (HR 0.91, 95%CI 0.74 to 1.13, P value = 0.39), but there was a positive relationship when we used fixed model (HR 0.85, 95%CI 0.78 to 0.93, P value = 0.004). For the incidence of liver cancer, there was no significant difference (HR 1.36, 95%CI 0.9 to 2.04, P value = 0.14), however, the result changed after we excluded Chiang’s 2012 study (HR 1.69, 95%CI 1.03 to 2.77, P value = 0.04). There was no significant difference in other types of cancer.ConclusionBased on current evidences, alendronate therapy may be associated with a high risk of lung cancer, may with an excess risk of liver cancer, a low risk of colorectal and no related risk of other cancers.

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Section: Resultsmentioning

confidence: 99%

“…Two of the studies were considered as having moderate comparability because they were only adjusted for two factors [13, 14]. Four included studies were judged as having mild outcome bias [5, 14–16]. …”

Section: Resultsmentioning

confidence: 99%

The Carcinogenicity of Alendronate in Patients with Osteoporosis: Evidence from Cohort Studies

et al. 2015

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“…There is evidence from controlled trials and observational studies that bisphosphonate treatment is associated with a decreased risk of breast cancer (45)(46)(47)(48), colorectal cancer (49), gastric cancer (50), stroke (51) and myocardial infarction (52) as well as improved survival (17,53).…”

Section: Possible "Side Benefits" Of Bisphosphonate Therapymentioning

confidence: 99%

Long-term risks of bisphosphonate therapy

Watts

2014

Arq Bras Endocrinol Metab

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The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a "drug holiday, " which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks. ReSumoO objetivo deste estudo foi resumir os riscos associados ao tratamento a longo prazo com bisfosfonatos. Foram pesquisadas as publicações médicas relevantes incluindo ensaios clíni-cos, extensões de ensaios clínicos, estudos observacionais e relatórios pós-comercialização (vigilância farmacológica). As extensões e modificações de ensaios clínicos não indicaram nenhuma situação de alarme quanto à segurança dos bisfosfonatos a longo prazo. Dados observacionais sugerem pelo menos tantos benefícios quanto riscos. Entretanto, relatos pós--comercialização de dor musculoesquelética, osteonecrose da mandíbula e fraturas de fêmur atípicas foram amplamente divulgados na imprensa leiga. O foco nos riscos a longo prazo do tratamento com bisfosfonatos tem sido pincipalmente a osteonecrose da mandíbula e as fraturas atípicas de fêmur. Essas últimas, embora mais frequentes (ainda que pouco comuns) em pacientes que receberam tratamento com bisfosfonatos por 5 anos ou mais, podem ocorrer em indivíduos não tratados com esses medicamentos. Pacientes com baixo risco de fratura podem potencialmente parar o tratamento depois de 3 a 5 anos ("drug holiday"). Esse procedimento reduz os riscos desses medicamentos a longo prazo. Não obstante, nos pacientes de maior risco a terapia por 6 a 10 anos parece ser aconselhável e oferece mais benefícios do que riscos.Arq Bras Endocrinol Metab. 2014;58(5):523-9

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“…Four epidemiological studies concentrating on breast cancer have shown positive effects for bisphosphonates: 32% RR reduction in postmenopausal women (HR 0.68, 95% CI 0.52 to 0.88),13 33% decreased risk in current users, women aged 20–69 years (OR 0.67, 95% CI 0.51 to 0.89),14 39% risk reduction in patients taking bisphosphonates for at least 1 year (OR 0.61, 95% CI 0.50 to 0.76)15 and 47% risk reduction after start of alendronate (HR 0.53, 95% CI 0.38 to 0.73) and 20% for etidronate (HR 0.80, 95% CI 0.73 to 0.89) 16. A study looking at the risk of endometrial cancer has also shown a 30% decrease associated with bisphosphonate use, but it was not statistically significant (OR 0.7, 95% CI 0.4 to 1.2) 17…”

Section: Introductionmentioning

confidence: 99%

Exposure to bisphosphonates and risk of cancer: a protocol for nested case–control studies using the QResearch primary care database

2012

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IntroductionBisphosphonates are becoming a common treatment for osteoporosis particularly after discovery of the association between hormone replacement therapy and increased risk of breast cancer. As osteoporosis develops with age, treatment is a long-term intervention. Randomised control trials typically have limited follow-up times, which restricts investigation of the effects of the drugs on risk of primary cancers. A few observational studies have demonstrated a reduced risk of breast cancer and possibly of endometrial cancer in bisphosphonate users. Two epidemiological studies have studied the effect of the drugs on oesophageal cancer but did not reach any definite conclusions. So far, no effects on colorectal and stomach cancer have been shown. This study will investigate the association of bisphosphonates with risks of the 10 most common primary cancers.Methods and analysisA series of nested case–control studies will be based on the general population using records from 660 UK general practices within the QResearch Database. Cases will be patients with primary cancers diagnosed between 1996 and 2011. Each case will be matched by age, sex, practice and calendar year to five controls, who are alive and registered with the practice at the time of diagnosis of the case. Exposure to bisphosphonates will be defined as at least one prescription during the study period. For the most common cancers with substantial numbers of observations, the effect of the duration of the treatment and different types of bisphosphonates will be studied. Conditional logistic regression will be applied to produce ORs adjusted for smoking status, socioeconomic status, ethnicity, cancer-specific co-morbidities and use of other medications.

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Use of Bisphosphonates and Risk of Breast Cancer

Cited by 38 publications

References 37 publications

The Carcinogenicity of Alendronate in Patients with Osteoporosis: Evidence from Cohort Studies

The Carcinogenicity of Alendronate in Patients with Osteoporosis: Evidence from Cohort Studies

Long-term risks of bisphosphonate therapy

Exposure to bisphosphonates and risk of cancer: a protocol for nested case–control studies using the QResearch primary care database

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