Tamoxifen exposure in relation to gastric adenocarcinoma development

Epidemiological research has indicated that the anti-oestrogen tamoxifen, used in breast cancer therapy, may increase the risk of gastric adenocarcinoma of the intestinal but not of the diffuse type. To test this hypothesis, and evaluate possible involvement of oestrogen receptors (ERs), we conducted a study amongst tamoxifen users and non-users. The study participants comprised women in the county of Stockholm who in the Swedish Cancer Register were first recorded with breast cancer and subsequently gastric cancer during the period January 1958-August 2005. Medical records were scrutinised to verify the diagnoses and classify into use or non-use of tamoxifen. Tumour material was reviewed histologically to verify gastric adenocarcinoma diagnosis and classify these cancers into intestinal or diffuse type. Intestinal adenocarcinomas were analysed immunohistochemically for the presence of ER alpha, beta and beta cx. Amongst 68 women with verified gastric adenocarcinoma, 30 had been treated with tamoxifen and 38 not. The intestinal type of gastric adenocarcinoma was not more frequent amongst tamoxifen users (27%) than amongst non-users (34%) (p=0.601). There were no material differences between the tamoxifen groups regarding distribution of any of the three ERs of the intestinal adenocarcinoma specimens. Tamoxifen users had a shorter latency between breast cancer and gastric adenocarcinoma (4 versus 13 years) which was similar in the intestinal and diffuse types. This study does not support the hypothesis that tamoxifen increases the isolated risk of the intestinal type, but it indicates that tamoxifen use might accelerate the tumour progression or increase the overall risk of gastric adenocarcinoma.