Relationship between histamine2-receptor antagonist medications and risk of invasive breast cancer

Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):67-72. doi: 10.1158/1055-9965.EPI-07-0765.


Background: Histamine(2)-receptor antagonist (H(2) blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H(2) blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H(2) blockers is a potential breast cancer risk factor. The few previous studies evaluating this association have been null but have been limited by small sample sizes, and none have evaluated risk by either histologic type or estrogen receptor/progesterone receptor status.

Methods: Combining data from two population-based case-control studies conducted in western Washington, we assessed the relationship between use of H(2) blockers and risk of different types of breast cancer among 1,941 cases and 1,476 controls 55 to 79 years old. Odds ratios and 95% confidence intervals (95% CI) were calculated using polytomous logistic regression.

Results: Current use of H(2) blockers overall, cimetidine, and famotidine was not associated with an increased risk of either invasive ductal or invasive lobular breast cancer. Current users of ranitidine had a 2.2-fold (95% CI, 1.1-4.3) increased risk of ductal carcinoma that was confined to a 2.4-fold (95% CI, 1.2-4.9) increased risk of estrogen receptor-positive/progesterone receptor-positive ductal carcinoma.

Conclusions: Use of H(2) blockers in general is not associated with an increased risk of breast cancer, although current use of ranitidine may increase risk of hormone receptor-positive ductal carcinoma. Further studies to confirm this finding are warranted.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Anti-Ulcer Agents / therapeutic use*
  • Breast Neoplasms / epidemiology*
  • Carcinoma, Ductal, Breast / epidemiology*
  • Carcinoma, Lobular / epidemiology*
  • Case-Control Studies
  • Cimetidine / therapeutic use
  • Famotidine / therapeutic use
  • Female
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Ranitidine / therapeutic use
  • Risk Factors
  • Washington / epidemiology


  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Famotidine
  • Cimetidine
  • Ranitidine