NEWS BRIEF
In a recent meta-analysis, women with schizophrenia who had long term exposure to antipsychotics were found to be at higher risk for breast cancer than both women with psychiatric disorders other than schizophrenia and women without psychiatric disorders.1
Chittaranjan Andrade, MD, Professor and Head of the Department of Psychopharmacology at the National Institute of Mental Health and Neurosciences, Bangalore, India, reviewed case-control, cohort and meta-analysis studies, that investigated the link between women with schizophrenia taking antipsychotic medications and breast cancer. Andrade reviewed 6 studies, including a meta analysis of 7 studies. The analysis also included a study examining the relationship between higher morbidity and mortality for women on antipsychotic medications undergoing breast cancer treatments. Literature on this topic has suggested women with schizophrenia are less likely to be screened for breast cancer, and after developing breast cancer, their mortality rates are higher.
One study showed exposure to aripiprazole, quetiapine, olanzapine, and ziprasidone were associated with increased risk of breast cancer (HR = 1.10).2 Amisulpride, paliperidone, risperidone, and zotepine were also associated with an increased risk of breast cancer (HR = 1.29). Generally, exposure to antipsychotic treatment was associated with an increased risk of breast cancer only beyond 6 years of observation in the study. Participant data was taken from a South Korean Health Insurance Review Agency database, with exposure group of 498,970 individuals and a comparison group of 997,940 individuals. Andrade pointed out that this study presented hazard ratios only, analysis did not adjust for confounds or covariates, and data matching was only based on age rather than index of first antipsychotic prescription.
Another study separated groups of women starting antipsychotic treatment with high and moderate prolactin-raising potential vs women starting antipsychotic treatment with low- and no-prolactin raising potential.3 Multiple analysis types were performed, with the sample size in the largest analysis being 13000, and analyses were adjusted for covariates. HRs for different analysis types ranged from 0.96 to 1.28. The study failed to find a statistically significant association between incident breast cancer and antipsychotic medications with high vs low prolactin raising potential.
Focusing on length of exposure to antipsychotic medications, Solmi et al found breast cancer was associated with increased odds of prior exposure to prolactin-increasing antipsychotics for both groups that took these medications for 1-4 years and 5 or more years. 4 The sample matched 1642 women with major mental illness who developed breast cancer with 8173 women without breast cancer. Matching was conducted based on age, type of psychiatric diagnosis, and length of illness. Exposure to prolactin-sparing antipsychotics (like clozapine, quetiapine, aripiprazole, brexpiprazole, cariprazine) was not found to be associated with increased risk of malignant breast cancer, regardless of exposure duration (OR=1.17 for 1-4 years and OR=0.99 for 5 or more years). Exposure to prolactin-raising antipsychotics for over 1 year was associated with increased risk.
In a markedly differing study, investigators included patients with psychiatric disorders other than schizophrenia (bipolar and major depressive disorder specifically) who had breast cancer. This study’s findings were notably different, finding that antipsychotic exposure may be protective against breast cancer.5 However, Andrade noted that elements of the study (small sample, no correction for false discovery rate, and short duration of medication exposure at 1-6 months) may account for this opposing finding. Importantly, Andrade was unaware of any other study with similar protective findings.
A recent study from 2025 followed patients for approximately 7 years and matched patients with new or existing schizophrenia to patients (N=224,612) with both non-schizophrenia psychiatric diagnoses (N=224,162) and women in the general population with no psychiatric disorders (N=449,224).6 This study used ICD-10 diagnosis criteria of invasive breast cancer or ductal carcinoma in situ to operationalize the variable of breast cancer presence in patients. The authors found a small but significant increase of new onset breast cancer in women with schizophrenia compared with both women with other psychiatric disorders (HR=1.07) and women with no psychiatric disorders (HR=1.26). This study also identified age differences for risk, finding that in age stratified analyses, only women in the perimenopausal age range (defined here as 40-64 years) were at an increased risk of new onset breast cancer (HR=1.17). Investigators also noted that antipsychotic treatment for 1 year was the point at which the risk for new onset breast cancer became statistically significant. Treatment longer than 1 year did not have progressively increasing risks.
Statistical significance emerged notably with first generation antipsychotics and prolactin-raising antipsychotics for treatment durations of more than 5 years. Nonetheless, a cause effect relationship could not be established from these observational studies. Andrade noted that because breast cancer is the most common form of cancer among women, “even a small increase in risk can translate into a large number of women affected in the population.” Andrade noted that clinicians should prefer second generation antipsychotics over first generation antipsychotics and prolactin-sparing antipsychotics over prolactin-raising antipsychotics.
Further research on the stage of breast cancer diagnosis in patients with schizophrenia compared to controls would provide information about whether this population should be screened earlier because of this higher risk. Studies which adequately adjust for covariates and compounds related to known risk factors for breast cancer should also be conducted, Andrade recommended.
“The results of studies in the field strongly recommend that women with schizophrenia, and especially those who require prolactin-raising antipsychotic for extended periods, need to be regularly screened or otherwise monitored for the risk of breast cancer,” Andrade wrote. “These women comprise a vulnerable population, and their medical health should not be neglected because caring for their mental health absorbs attention and time.”
References
1. Andrade C. Schizophrenia, antipsychotic drugs, and risk of breast cancer. J Clin Psychiatry. 2025;86(3):25f15960.
2. Joo SW, Lee BC, Lee J, et al. Risk of breast cancer in association with the use of second-generation antipsychotics. Clin Psychopharmacol Neurosci. 2022;20(4):675-684.
3. Kern DM, Shoaibi A, Shearer D, et al. Association between prolactin increasing antipsychotic use and the risk of breast cancer: a retrospective observational cohort study in a United Stated Medicaid population. Front Oncol. 2024;24:1356640.
4. Solmi M, Lahteenvuo M, Tanskanen A, et al. Antipsychotic use and risk of breast cancer in women with severe mental illness: replication of a nationwide nested case-control database study. Schizophr Bull. 2024;50(6):1471-1481.
5. Li DJ, Tsai SJ, Chen TJ, et al. Exposure to psychotropic drugs and breast cancer risk in patients with bipolar disorder and major depressive disorder: a nested case-control study. Eur Arch Psychiatry Clin Neurosci. 2025;275(2):533-543.
6. Yang JS, Kang S, Kim K, et al. Breast cancer risk among women with schizophrenia and association with duration of antipsychotic use: population based cohort study in South Korea. Br J Psychiatry. 2025;226(4):206-212.