Use of antipsychotics and risk of breast cancer: a Danish nationwide case-control study

Br J Clin Pharmacol. 2018 Sep;84(9):2152-2161. doi: 10.1111/bcp.13661. Epub 2018 Jul 8.


Aims: Some antipsychotics increase prolactin levels, which might increase the risk of breast cancer. Existing evidence is conflicting and based on sparse data, especially for the increasingly used second-generation antipsychotics. We conducted a nationwide case-control study of the association between antipsychotic use and incident breast cancer.

Methods: From the Danish Cancer Registry, we identified women with a first-time diagnosis of breast cancer 2000-2015 (n = 60 360). For each case, we age-matched 10 female population controls. Using conditional logistic regression, we calculated odds ratios (ORs) for breast cancer associated with use of antipsychotics. We stratified antipsychotics by first- and second-generation status and by ability to induce elevation of prolactin.

Results: In total, 4951 cases (8.1%) and 47 643 controls (7.9%) had ever used antipsychotics. Long-term use (≥10 000 mg olanzapine equivalents) was associated with breast cancer, with an adjusted OR of 1.18 [95% confidence interval (CI), 1.06, 1.32]. A weak dose-response pattern was seen, with ORs increasing to 1.27 (95% CI 1.01, 1.59) for ≥50 000 mg olanzapine equivalents. Associations were similar for first- and second-generation antipsychotics (ORs 1.17 vs. 1.11), but also for nonprolactin inducing-antipsychotics (OR 1.17). Stratifying by oestrogen receptor status, positive associations were seen for oestrogen receptor-positive cancers (long-term use: OR 1.29; 95% CI 1.13, 1.47) while no associations were observed for oestrogen receptor-negative cancers.

Conclusions: Overall, our results do not suggest a clinically important association between antipsychotic use and risk of breast cancer. The importance of drug-induced prolactin elevation is unclear but may lead to a slightly increased risk of oestrogen receptor-positive breast cancer.

Keywords: antipsychotics; breast cancer; pharmacoepidemiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Breast Neoplasms / blood
  • Breast Neoplasms / chemically induced
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Denmark / epidemiology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Incidence
  • Logistic Models
  • Middle Aged
  • Odds Ratio
  • Prolactin / blood*
  • Prolactin / metabolism
  • Receptors, Estrogen / metabolism
  • Registries / statistics & numerical data*
  • Time Factors


  • Antipsychotic Agents
  • Receptors, Estrogen
  • Prolactin