Use of antipsychotics and risk of breast cancer: a Danish nationwide case–control study

Pottegård, Anton; Lash, Timothy L.; Cronin‐Fenton, Deirdre; Ahern, Thomas P.; Damkier, Per

doi:10.1111/bcp.13661

Cited by 39 publications

(64 citation statements)

References 50 publications

(66 reference statements)

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“…6 mg/day) . The considerable use of olanzapine might be problematic, besides its propensity to lead to metabolic side effects, as high cumulative doses of olanzapine have also been associated with a slightly increased risk of breast cancer in a recent case–control study . Bachmann and colleagues also found similar stable or slightly increasing prevalence of clozapine use in the Scandinavian countries as well as other countries, suggesting that clozapine is reserved for treatment of severe mental illness …”

Section: Discussionmentioning

confidence: 96%

Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016

Pottegård

Johnsen

Kroken

et al. 2019

Brit J Clinical Pharma

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Aims: The aim of this study was to investigate time trends in dosing and prevalence of antipsychotic prescriptions in Scandinavia.Methods: We retrieved data on antipsychotic use between 2006 and 2016 from Danish, Norwegian and Swedish national prescription registers. For each antipsychotic, we calculated prevalence of use and mean doses, overall and for specific age groups (young, adults and elderly). Results: Antipsychotic use in Scandinavia increased from 16.5 to 17.2 users/1000 inhabitants between 2006 and 2016 (+2.4%, annual change: 0.07 users/1000 inhabitants/year, 95% CI: 0.02-0.20, P = 0.02). In 2006, chlorprothixene and levomepromazine were the most commonly used antipsychotics. By 2016, quetiapine was the most used antipsychotic in all three countries and across all age groups, with an overall 1-year prevalence of 4.05-9.97 users/1000 inhabitants (annual change: 0.57 users/1000 inhabitants/year, 95% CI: 0.54-0.60, P < 0.001). Quetiapine showed a marked decrease in mean doses during the 11-year study period (0.46-0.28 defined daily doses (DDD)/user/day: 39.1%, −0.02 DDD/user/day/year, 95% CI: −0.020 to −0.015, P < 0.001). In 2016, the highest mean doses were seen for clozapine (0.90-1.07 DDD/user/day) and olanzapine (0.66-0.88 DDD/user/day).Conclusions: There is an increased prevalence of antipsychotic prescriptions that coincides with low and/or decreasing mean doses of the majority of commonly used antipsychotics in Scandinavia. Of all antipsychotics, this development was most pronounced for quetiapine. Reasons for and consequences of increased antipsychotic use that lasts shorter periods of time requires further study.

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Section: Discussionmentioning

confidence: 96%

Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016

Pottegård

Johnsen

Kroken

et al. 2019

Brit J Clinical Pharma

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“…However, several other studies report no dependence in the breast cancer rate and the use of antidepressant/antipsychotic drugs. For instance, a recently conducted study in Denmark on 4,951 antipsychotic users and 47,643 non-users found no clinically important association between the antipsychotic drug use and risk of breast cancer [ 160 ]. Two other earlier studies conducted in Denmark and UK, already mentioned in this section, also found that the rate of breast cancer is unaffected by the use of antidepressants [ 155 , 157 ].…”

Section: Population Studies Of the Effect Of Antipsychotic Medication On Cancer Riskmentioning

confidence: 99%

Multifaceted effect of chlorpromazine in cancer: implications for cancer treatment

Kamgar-Dayhoff

Brelidze

2021

Oncotarget

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Since its discovery in 1951, chlorpromazine (CPZ) has been one of the most widely used antipsychotic medications for treating schizophrenia and other psychiatric disorders. In addition to its antipsychotic effect, many studies in the last several decades have found that CPZ has a potent antitumorigenic effect. These studies have shown that CPZ affects a number of molecular oncogenic targets through multiple pathways, including the regulation of cell cycle, cancer growth and metastasis, chemo-resistance and stemness of cancer cells. Here we review studies on molecular mechanisms of CPZ's action on key proteins involved in cancer, including p53, YAP, Ras protein, ion channels, and MAPKs. We discuss common and overlapping signaling pathways of CPZ's action, its cancer-type specificity, antitumorigenic effects of CPZ reported in animal models and population studies on the rate of cancer in psychiatric patients. We also discuss the potential benefits and limitations of repurposing CPZ for cancer treatment.

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“…There have been several reports on the relationship between breast cancer and antipsychotics [ 3 ], and higher blood prolactin levels are associated with a higher risk of breast cancer, especially hormone receptor-positive and postmenopausal breast cancers [ 5 ]. A case-control study examining the association between antipsychotic drug use and breast cancer development found that there was no association between antipsychotic drug use and breast cancer risk but that there may be a slightly increased risk for ER-positive breast cancer [ 6 ]. However, there are reports that deny the association between breast cancer and the use of antipsychotics [ 7 , 8 ], and no conclusions on this matter have been reached.…”

Section: Introductionmentioning

confidence: 99%

Effect of antipsychotics on breast tumors by analysis of the Japanese Adverse Drug Event Report database and cell-based experiments

Maeshima

Iijima

Watanabe

et al. 2021

J Pharm Health Care Sci

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Background Since antipsychotics induce hyperprolactinemia via the dopamine D2 receptor, long-term administration may be a risk factor for developing breast tumors, including breast cancer. On the other hand, some antipsychotic drugs have been reported to suppress the growth of breast cancer cells in vitro. Thus, it is not clear whether the use of antipsychotics actually increases the risk of developing or exacerbating breast tumors. The purpose of this study was to clarify the effects of antipsychotic drugs on the onset and progression of breast tumors by analyzing an adverse event spontaneous reporting database and evaluating the proliferation ability of breast cancer cells. Methods Japanese Adverse Drug Event Report database (JADER) reports from April 2004 to April 2019 were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. Reports of females only were analyzed. Adverse events included in the analysis were hyperprolactinemia and 60 breast tumor-related preferred terms. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) were used to detect signals. Furthermore, MCF-7 cells were treated with haloperidol, risperidone, paliperidone, sulpiride, olanzapine and blonanserin, and cell proliferation was evaluated by WST-8 assay. Results In the JADER analysis, the IC signals of hyperprolactinemia were detected with sulpiride (IC, 3.73; 95% CI: 1.81–5.65), risperidone (IC, 3.69; 95% CI: 1.71–5.61), and paliperidone (IC, 4.54; 95% CI: 2.96–6.12). However, the IC signal of breast tumors was not observed with any antipsychotics. In cell-based experiments, MCF-7 cells were treated with six antipsychotics at concentrations of 2 and 32 μM, and none of the drugs showed any growth-promoting effects on MCF-7 cells. On the other hand, blonanserin markedly suppressed the growth of MCF-7 cells at a concentration of 32 μM, and the effect was concentration dependent. Conclusions Analysis of the JADER using the IC did not show breast tumor signals due to antipsychotic drugs. In in vitro experiments, antipsychotics did not promote MCF-7 cell proliferation whereas blonanserin suppressed MCF-7 cell growth. Further research on the effects of blonanserin on the onset and progression of breast tumor is expected.

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Use of antipsychotics and risk of breast cancer: a Danish nationwide case–control study

Abstract: Overall, our results do not suggest a clinically important association between antipsychotic use and risk of breast cancer. The importance of drug-induced prolactin elevation is unclear but may lead to a slightly increased risk of oestrogen receptor-positive breast cancer.

Cited by 39 publications

References 50 publications

Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016

Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016

Multifaceted effect of chlorpromazine in cancer: implications for cancer treatment

Effect of antipsychotics on breast tumors by analysis of the Japanese Adverse Drug Event Report database and cell-based experiments

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