Antipsychotics Linked to Increased Breast Cancer Risk

Long-term exposure to prolactin-increasing antipsychotics increases the odds of developing breast cancer.

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A new study in The Lancet Psychiatry revealed that certain antipsychotics might increase breast cancer risk in women diagnosed with schizophrenia.

A team of Finnish researchers utilized nationwide data of all individuals diagnosed with schizophrenia in inpatient care over the course of four decades to assess cumulative exposure to different types of antipsychotics and the associated risk of developing breast cancer.

“To our knowledge,” the research team wrote, “this is the first study on the risk of breast cancer within a cohort of patients with schizophrenia including a sufficiently high cumulative antipsychotic exposure to assess the putative increased risk of breast cancer related to the use of prolactin-increasing antipsychotics.”

Women diagnosed with schizophrenia are at increased risk of developing breast cancer. Moreover, underdiagnosis and delayed treatment for breast cancer may contribute to higher mortality rates in this population.

Although women with schizophrenia are more likely to present with conditions that increase breast cancer risks, such as obesity, diabetes, and substance use, preliminary research has indicated that exposure to antipsychotic drugs may also play a role.

Certain antipsychotic drugs lead to higher concentrations of prolactin, a hormone associated with heightened risk for developing breast cancer. Some research evidence has demonstrated a significant connection between antipsychotics and breast cancer risk. However, these studies did not clearly distinguish prolactin-increasing antipsychotics from other types (e.g., “prolactin-sparing” antipsychotics, including aripiprazole, quetiapine, clozapine). In addition, these studies did not control for confounding variables, or they lacked sufficient statistical power to draw robust conclusions.

A team of researchers led by Heidi Taipale aimed to determine whether exposure to prolactin-increasing antipsychotic drugs contributed to increased odds of developing breast cancer. The team used Finnish nationwide register-based data to compare women diagnosed with schizophrenia and breast cancer to women with schizophrenia who were not diagnosed with breast cancer. They utilized a nested case-control study to control for age and duration of illness. They adjusted for risk factors including diabetes, substance use, number of children, and exposure to other medications that can augment breast cancer risk.

They found that long-term exposure (5+ years) to prolactin-increasing antipsychotics significantly increased the risk of developing breast cancer, with 56% higher odds than shorter exposure. No association with breast cancer was observed in patients exposed to prolactin-sparing antipsychotics.

They wrote:

“In conclusion, long-lasting exposure to prolactin-increasing antipsychotics might increase the risk of breast cancer in women in schizophrenia.”

Taipale and their team attributed the increased breast cancer risk to excess prolactin, an established effect of antipsychotic drugs. However, despite this established effect of antipsychotics, the evidence that excess prolactin is associated with an elevated risk of developing breast cancer “is inconclusive, despite plausibility,” they noted.

This study included notable strengths, such as nationwide data that captured all individuals diagnosed with schizophrenia in inpatient care over the course of four decades. The team also articulated several limitations of their study, including that they were unable to adjust for smoking status and obesity and assess risk owing to estrogen-receptor status, family history, and genetic mutations. In addition to this, the relatively recent introduction of aripiprazole to the Finnish market in 2004 meant that they could not analyze its risk, along with other newer antipsychotic drugs, including brexpiprazole, cariprazine, and lumateperone.

The researchers interpreted their findings as clinically meaningful, offering recommendations to limit patients’ long-term exposure to prolactin-increasing antipsychotics, monitor prolactin concentrations, and utilize proper cancer screening in women diagnosed with schizophrenia to promote early detection and treatment for breast cancer.

 

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Taipale, H., Solmi, M., Lähteenvuo, M., Tanskanen, A., Correll, C. U., & Tiihonen, J. (2021). Antipsychotic use and risk of breast cancer in women with schizophrenia: a nationwide nested case-control study in Finland. The Lancet Psychiatry. https://doi.org/10.1016/S2215-0366(21)00241-8

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