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

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)