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Psychiatry Research Review

Sanjay Gupta, MD
Released: November 18, 2021

Antipsychotics, Schizophrenia, Prolactin, and Breast Cancer Risk: Finnish Study

Taipale H, et al. Lancet Psychiatry. 2021;8:883-891.

Background
Female patients with schizophrenia have a higher incidence of breast cancer compared with the general population. It has been suggested that D2-receptor–targeting antipsychotics are associated with a higher risk of breast cancer due to their ability to increase prolactin, a known risk factor for the development of breast cancer.

Methods                                           
Data for women diagnosed with schizophrenia, both with and without breast cancer, were obtained from Finnish nationwide registers of hospital treatment and prescription purchases. Women between 18 and 85 years of age with breast cancer (cases) were matched with women without breast cancer (controls) who were of a similar age and had a similar duration of illness. Women were excluded from analysis if they previously had received a cancer diagnosis, were recipients of an organ transplant, had been diagnosed with HIV, or had undergone a mastectomy. Logistic regression adjusting for comorbid conditions and concomitant medications was used to assess whether exposure to prolactin-increasing antipsychotics was associated with increased risk of breast cancer.

Results
Between 1972 and 2014, 30,785 women were diagnosed with schizophrenia, and 1069 went on to be diagnosed with breast cancer between January 1, 2000, and December 31, 2017. Based on comparison with the 5339 matched controls, long-term cumulative treatment with prolactin-sparing antipsychotics was not associated with an increased risk of breast cancer. Treatment with prolactin-increasing antipsychotics for ≥5 years was associated with a significantly increased risk of breast cancer vs <1 year of treatment, with a higher risk of developing lobular adenocarcinoma than ductal adenocarcinoma.

Conclusions
Women with schizophrenia who had a long cumulative exposure to prolactin-increasing antipsychotics were at increased risk of breast cancer. Monitoring prolactin levels and treating hyperprolactinemia is paramount in women receiving prolactin-increasing antipsychotics to reduce their risk for breast cancer.

Clinical Commentary
Breast cancer is the most common cancer in women, with a lifetime prevalence of 12%. Patients with schizophrenia have an even higher risk of breast cancer, with an incidence 25% higher compared with the general population. Breast cancer may also be underdiagnosed in women with schizophrenia, as barriers to accessing preventive healthcare and/or primary care physicians reduce screening. This study had a large sample size and case-control design, and patients receiving clozapine were also included. It is the first study to report an increased risk of breast cancer in women with long cumulative exposure to prolactin-increasing antipsychotics. The limitations of this study were that ethnicity data were not available, and the analysis was not adjusted for obesity, smoking status, or estrogen receptor status.

Clinical Insights

  • Women with ≥5 years of exposure to prolactin-increasing antipsychotics had 56% higher odds of developing breast cancer than shorter exposure.
  • A higher risk was not observed in women exposed to prolactin-sparing antipsychotics, regardless of the length of exposure.
  • The fact that patients with schizophrenia have a higher prevalence of breast cancer heightens the importance of these findings.
  • Prolactin-increasing antipsychotics elevated the risk for both lobular adenocarcinoma and ductal adenocarcinoma, with the highest risk for lobular adenocarcinoma.

Summary
In my professional opinion, psychiatrists or other members of the mental health team should cotrack breast cancer screenings with primary care. Healthcare professionals should preferentially use the prolactin-sparing antipsychotics (aripiprazole, brexpiprazole, lumateperone, cariprazine, quetiapine, and clozapine) and avoid first-generation agents and prolactin-increasing antipsychotics (risperidone, paliperidone, and lurasidone). Prolactin levels should be measured, and hyperprolactinemia should be addressed by switching to a prolactin-sparing agent.

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