Summary: A systematic review and meta-analysis finds a moderate association between antipsychotic use and an increased risk of breast cancer.
Source: University of Hong Kong
A research team from the Center for Safe Medication Practice and Research (CSMPR), Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong (HKUMed) conducted the world’s first systematic review and meta-analysis of observational studies involving over 2 million people and estimated a moderate association—an elevated breast cancer risk of more than 30%—among antipsychotic users.
These findings emphasize the need for careful risk–benefit evaluation when prescribing antipsychotics, particularly for patients with existing risk factors for breast cancer. The full results appear in Epidemiology and Psychiatric Sciences.
Antipsychotic medicines are widely used to treat conditions such as schizophrenia, bipolar disorder, major depressive disorder and, in some cases, symptoms of dementia. Prior research consistently shows higher breast cancer rates among people with schizophrenia and bipolar disorder, and antipsychotic exposure has been suggested as one possible contributor to that excess risk.
Potential biological and behavioral mechanisms linking antipsychotic treatment to breast cancer include drug-induced hyperprolactinemia, medication-related weight gain and associated metabolic changes, and lifestyle factors that may be more common among people taking these medications.
Because the relationship is biologically complex and influenced by many interacting factors, available evidence has been inconclusive. To clarify the association, the CSMPR team performed a systematic review and meta-analysis of observational studies to synthesize current data and quantify any link between antipsychotic use and breast cancer.
Research findings
The review included nine observational studies with a combined total of 2,031,380 adults: five cohort studies and four case-control studies. Seven of those studies were eligible for pooled meta-analysis, covering 1,557,013 participants. All included studies were rated high-quality (scoring seven to nine stars on the Newcastle–Ottawa Scale).
Six of the nine studies reported a statistically significant association between antipsychotic use and increased breast cancer incidence. Pooled estimates from cohort studies (hazard ratios) and case-control studies (odds ratios) indicated a moderate positive association: a pooled HR of 1.39 (95% CI 1.11–1.73) and a pooled OR of 1.37 (95% CI 0.90–2.09). Overall, the meta-analysis suggests an increased breast cancer risk of roughly 30% among antipsychotic users.
Some studies also found that greater cumulative exposure—such as longer duration of antipsychotic use—was associated with higher breast cancer risk. The review highlighted evidence particularly implicating antipsychotics known to raise prolactin levels. For example, a large Finnish case-control study that used electronic health records compared prolonged exposure to prolactin-elevating antipsychotics with shorter exposure (under one year) and reported an almost 60% higher risk for those with at least five years of exposure.
Although observational studies can be limited by unmeasured confounding and other biases, the consistency across high-quality studies supports the conclusion that breast cancer may be a rare but clinically meaningful adverse outcome associated with antipsychotic use.
Biological pathways that may explain the elevated risk include hyperprolactinemia induced by some antipsychotics and downstream metabolic complications such as central obesity, diabetes and cardiovascular disease, which can themselves influence cancer risk.
“With the expanding and sometimes off-label use of antipsychotics worldwide, clinicians should undertake a thorough clinical assessment of individual patients and consider the overall safety profile of antipsychotic agents before prescribing,” said Dr. Francisco Lai Tsz-tsun, Research Assistant Professor, Department of Pharmacology and Pharmacy, HKUMed, and corresponding author of the study.
Based on these results, clinicians should preferentially avoid antipsychotics known to elevate prolactin in patients who carry breast cancer risk factors. Where such medications are considered necessary, patients should receive counseling about potential risks and clinicians may consider measuring baseline and follow-up prolactin levels, with prompt management if hyperprolactinemia occurs.
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Source: University of Hong Kong
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Original Research: Open access. “Association of antipsychotic use with breast cancer: a systematic review and meta-analysis of observational studies with over 2 million individuals” by Janice Ching Nam Leung et al., published in Epidemiology and Psychiatric Sciences.
Abstract
Association of antipsychotic use with breast cancer: a systematic review and meta-analysis of observational studies with over 2 million individuals
Aims
Reports have suggested an elevated breast cancer risk among women treated with antipsychotics, but findings have been inconsistent. This study aimed to systematically review observational evidence and evaluate the hypothesized association between antipsychotic exposure and breast cancer.
Methods
The authors searched Embase, PubMed and Web of Science databases (search conducted 27 January 2022) for cohort and case-control studies from database inception, supplemented by manual searches of references. Study quality was assessed with the Newcastle–Ottawa Scale. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated using random-effects models. The review was registered with PROSPERO (CRD42022307913).
Results
Nine observational studies (five cohort, four case-control) comprising 2,031,380 participants were included in the review; seven studies (1,557,013 participants) were pooled in meta-analysis. All studies were rated high-quality (seven to nine stars). Six studies reported a significant association between antipsychotic use and breast cancer, and stronger associations were observed with greater extents of exposure, such as longer duration. Pooled HRs from cohort studies and ORs from case-control studies were 1.39 (95% CI 1.11–1.73) and 1.37 (95% CI 0.90–2.09), respectively, indicating a moderate association.
Conclusions
Antipsychotic use appears to be moderately associated with an increased risk of breast cancer, potentially mediated in part by prolactin-elevating properties of some medications. Clinicians should weigh this risk against potential therapeutic benefits when making prescribing decisions and consider monitoring and preventive measures for at-risk patients.