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Relationship between Histamine₂-Receptor Antagonist Medications and Risk of Invasive Breast Cancer

Divisions of ¹ Public Health Sciences and ² Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington

Requests for reprints: Robert W. Mathes, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-C308, P.O. Box 19024, Seattle, WA, 98109-1024. Phone: 206-667-5265; Fax: 206-667-5948. E-mail: rmathes{at}u.washington.edu

Background: Histamine₂-receptor antagonist (H₂ blocker) medications are used to treat heartburn, gastroesophageal reflux disease, and ulcers. Some H₂ blockers, specifically cimetidine and ranitidine, also increase serum prolactin concentrations. Given the positive relationship between prolactin levels and postmenopausal breast cancer risk, use of H₂ 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 H₂ 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 H₂ 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 H₂ 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. (Cancer Epidemiol Biomarkers Prev 2008;17(1):67–72)