Desloratadine and loratadine stand out among common H1-antihistamines for association with improved breast cancer survival

Acta Oncol. 2020 Sep;59(9):1103-1109. doi: 10.1080/0284186X.2020.1769185. Epub 2020 May 27.

Abstract

Background: As tumors maintain an inflammatory microenvironment, anti-inflammatory medication can be useful in cancer therapy. We have previously shown an association with improved survival in melanoma for use of the H1-antihistamines desloratadine and loratadine, and here we examine use of H1-antihistamines and breast cancer mortality.

Material and methods: We investigated use of the six major H1-antihistamines (cetirizine, clemastine, desloratadine, ebastine, fexofenadine and loratadine) and breast cancer-specific and overall mortality in a nation-wide register-based study of all 61,627 Swedish women diagnosed with breast cancer 2006-2013. Both peri- and post-diagnostic antihistamine use was analyzed using Cox regression models. Analyses were stratified for age and subgroup analyses based on estrogen receptor status and menopausal status were performed.

Results: We found a consistently improved survival of desloratadine users (HR = 0.67; 95% CI 0.55-0.81, p < .001), as well as of loratadine users (HR = 0.80; 95% CI 0.67-0.95, p = .012), relative to nonusers, regardless of patient age, menopause, estrogen receptor status or stage of the tumor, or whether breast cancer-specific or overall survival was analyzed. The survival of users of other antihistamines varied relative to non-users.

Conclusion: Based on their safety and current use within the patient population, together with our observations, we suggest the initiation of trials of desloratadine and loratadine as treatment of breast cancer as well as studies of the mechanism behind their possible effect. Further studies on any effects of other H1-antihistamines may also be merited, as well as of H1-antihistamine use and survival in other malignancies.

MeSH terms

  • Breast / drug effects
  • Breast / immunology
  • Breast / pathology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Drug Prescriptions / statistics & numerical data*
  • Female
  • Follow-Up Studies
  • Histamine H1 Antagonists, Non-Sedating / administration & dosage*
  • Humans
  • Loratadine / administration & dosage
  • Loratadine / analogs & derivatives*
  • Middle Aged
  • Receptors, Estrogen / metabolism
  • Registries / statistics & numerical data
  • Risk Assessment / statistics & numerical data
  • Risk Factors
  • Survival Analysis
  • Survival Rate
  • Sweden / epidemiology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Histamine H1 Antagonists, Non-Sedating
  • Receptors, Estrogen
  • Loratadine
  • desloratadine