A research team from the Centre for Safe Medication Practice and Research (CSMPR) in the Department of Pharmacology and Pharmacy at the University of Hong Kong (HKUMed) conducted a systematic review and meta-analysis of observational studies with over 2 million individuals and estimated a moderate association between antipsychotic use and breast cancer risk. This finding highlights the importance of the risk-benefit assessment of antipsychotic prescription in high-risk patients. The research was published by Leung et al in Epidemiology and Psychiatric Sciences.

Analysis Background

Antipsychotics are commonly prescribed for patients with a range of psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and dementia. Elevated breast cancer incidence has been consistently reported in patients with schizophrenia and bipolar disorder, and it was speculated that antipsychotic use may potentially explain at least part of the increased risk. Possible mechanisms include antipsychotic-induced hyperprolactinemia, antipsychotic-mediated weight gain, and poorer lifestyle among antipsychotic users.

With complex mechanisms and multiple interacting risk factors, the evidence of said association remained inconclusive. Therefore, researchers from CSMPR systematically reviewed and conducted a meta-analysis to synthesize the existing evidence and determine the association between antipsychotic use and breast cancer.

Research Findings

Nine observational studies including over 2 million adults (five cohort and four case-control studies) were included for the review, and seven were included in the meta-analysis. All these studies were rated as high-quality according to the Newcastle-Ottawa Scale, a standardized study quality assessment instrument.

This review found that six of the nine studies had reported a significant association between the use of antipsychotic medications and an increased risk of breast cancer. The meta-analysis estimated a moderate positive association of an elevated risk of more than 30% among antipsychotic users. Pooled estimates of adjusted hazard ratios extracted from cohort studies and adjusted odds ratios from case-control studies were 1.39 (95% confidence interval [CI] = 1.11–1.73] and 1.37 (95% CI = 0.90–2.09). Some reviewed evidence further showed the extent of antipsychotic exposure, such as a longer duration of use, was associated with a higher risk of breast cancer, particularly for antipsychotics with prolactin-elevating properties. For example, a large Finnish case-control study used electronic health records to compare prolonged periods of prolactin-increasing antipsychotic use to those exposed for less than a year, which showed a significantly increased risk among those exposed for at least 5 years by nearly 60% (odds ratio = 1.56, 95% CI = 1.27–1.92).

Despite some limitations, such as unmeasured confounding effects, this study highlighted that breast cancer could be a potential but rare adverse event of antipsychotic medications. The elevated breast cancer risk may be explained by hyperprolactinemia and other complications possibly induced by antipsychotics, such as central obesity, diabetes, and cardiovascular disease.

“With the increasingly prevalent use of antipsychotics worldwide, including off-label use, we believe a comprehensive clinical assessment should be made for patients based on the overall safety profile of antipsychotics before prescription,” commented Francisco Lai Tsz-tsun, PhD, Research Assistant Professor in the Department of Pharmacology and Pharmacy at HKUMed and the corresponding author of the study.

Based on the findings of this study, antipsychotics with known prolactin-elevating properties should preferably be avoided in patients with risk factors of breast cancer. Appropriate counseling is warranted before prescribing prolactin-elevating antipsychotics, and prolactin level monitoring may be considered. Prompt management of antipsychotic-induced hyperprolactinemia is essential.

Disclosure: This work was partially supported by the Laboratory of Data Discovery for Health (D24H) under the AIR@InnoHK established by the Innovation and Technology Commission, the Government of Hong Kong Special Administrative Region. For full disclosures of the study authors, visit cambridge.org.