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Some Antipsychotics Elevate Breast Cancer Risk, a Large Study Confirms

Worst Pills, Best Pills Newsletter article July, 2022

Many antipsychotic medications block dopamine, a chemical messenger in the brain known as a neurotransmitter.[1] Inhibition of dopamine not only affects emotions and thoughts, it also promotes release of the hormone prolactin from the pituitary gland (a pea-sized structure at the base of the brain).[2] Prolactin stimulates breast cells to proliferate and produce milk.[3],[4]

Observational studies have found that increased prolactin levels are associated with an increased breast cancer...

Many antipsychotic medications block dopamine, a chemical messenger in the brain known as a neurotransmitter.[1] Inhibition of dopamine not only affects emotions and thoughts, it also promotes release of the hormone prolactin from the pituitary gland (a pea-sized structure at the base of the brain).[2] Prolactin stimulates breast cells to proliferate and produce milk.[3],[4]

Observational studies have found that increased prolactin levels are associated with an increased breast cancer risk.[5] Breast cancer is the most common cancer among women. In 2018, there were over 250,000 new female breast cancer cases and 42,000 breast cancer-related deaths in the U.S.[6]

Many studies have suggested that breast cancer risk, via prolactin elevation, is increased by antipsychotic medications, but the results were mixed and warranted further, more rigorous investigation.

A recent, large observational study has added stronger evidence that certain antipsychotic medications increase breast cancer risk.

The new observational study[7]

The new study, which was published in the January/February 2022 issue of the Journal of Clinical Pharmacology, was based on an analysis of commercial and Medicaid insurance claims to assess whether there was a link between antipsychotic use and subsequent new breast cancer cases.

The researchers classified all antipsychotics in their database as having high, medium or low propensity to cause prolactin elevation (see Table, below).

Propensity of Antipsychotics to Cause Prolactin Elevation

Propensity Level Generic Name Brand Name(s)†
High chlorpromazine* generic only
fluphenazine* generic only
haloperidol* generic only
loxapine* generic only
molindone* generic only
paliperidone* INVEGA
perphenazine* generic only
pimozide generic only
prochlorperazine* PROCOMP
risperidone* RISPERDAL
thioridazine** generic only
trifluoperazine* generic only
Medium iloperidone** FANAPT
lurasidone* LATUDA
olanzapine* ZYPREXA
Low chlorpromazine* generic only
aripiprazole* ABILIFY
asenapine* SAPHRIS
brexpiprazole* REXULTI
cariprazine* VRAYLAR
clozapine* CLOZARIL, VERSACLOZ
quetiapine* SEROQUEL
ziprasidone** GEODON

†Brand-name combination products were excluded, and only oral brand-name products listed.
*Designated as Limited Use by
Worst Pills, Best Pills News
**Designated as Do Not Use by Worst Pills, Best Pills News

They analyzed data from insurance-claims records spanning 10 years (2007 to 2016), corresponding to the medical care of more than 150 million privately insured patients and 20 million Medicaid-insured patients in the U.S. The researchers selected a subsample of 540,737 women who met the following criteria: 12 months of continuous insurance enrollment before the first prescription of an antipsychotic or a comparison seizure or bipolar medication, no prior history of breast cancer and age 18 to 64 years. Comparison drugs were selected because they are used to treat psychiatric or neurologic diseases but do not cause elevations in prolactin.

During the study observation period, the researchers identified 914 women (0.2%) who subsequently developed invasive breast cancer among the 540,737 included in the study. Women exposed to high-propensity prolactin-elevating antipsychotics had a statistically significant 62% increased risk of developing breast cancer compared with those treated with comparison drugs, and women exposed to medium-propensity prolactin-elevating antipsychotics had a statistically significant 54% increased risk. Women exposed to low-propensity prolactin-elevating drugs did not have an increased risk of breast cancer. These analyses were adjusted for cumulative drug dose, age and other risk factors for breast cancer including smoking, alcohol abuse and obesity.

What You Can Do

Be aware that certain antipsychotic medications may increase your risk of breast cancer, although the absolute increase in risk is low. If you are on long-term treatment with an antipsychotic that has a high or medium propensity to cause elevated prolactin levels and have a high risk of breast cancer based on other factors, talk to your doctor about whether you should switch to an antipsychotic with a low propensity to cause elevated prolactin levels.

Finally, ask your doctor about breast cancer screening, which is generally recommended every other year for women older than age 50.[8]
 



References

[1] Snyder PJ. Causes of hyperprolactinemia. UpToDate. October 29, 2021.

[2] Rahman T, Sahrmann JM, Olsen MA, et al. Risk of breast cancer with prolactin elevating antipsychotic drugs: an observational study of US women (ages 18-64 Years). J Clin Psychopharmacol. 2022;42(1):7-16.

[3] Redman B, Kitchen C, Johnson KW et al. Levels of prolactin and testosterone and associated sexual dysfunction and breast abnormalities in men with schizophrenia treated with antipsychotic medications. J Psychiatr Res. 2021 Nov;143:50-53.

[4] Wu Z, Li Q, Yang S, et al. Energy deprivation-induced AMPK activation inhibits milk synthesis by targeting PrlR and PGC-1α. Cell Commun Signal. 2022 Mar 5;20(1):25.

[5] Rahman T, Sahrmann JM, Olsen MA, et al. Risk of breast cancer with prolactin elevating antipsychotic drugs: an observational study of US women (ages 18-64 Years). J Clin Psychopharmacol. 2022;42(1):7-16.

[6] U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on 2020 submission data (1999-2018): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; www.cdc.gov/cancer/dataviz, released in June 2021. Accessed April 20, 2022.

[7] Rahman T, Sahrmann JM, Olsen MA, et al. Risk of breast cancer with prolactin elevating antipsychotic drugs: an observational study of US women (ages 18-64 Years). J Clin Psychopharmacol. 2022;42(1):7-16.

[8] U.S. Preventive Services Task Force. Final recommendation statement: Breast cancer: Screening. January 11, 2016. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening. Accessed May 6, 2022.