Re: the p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry.

juvant tamoxifen therapy for early stage breast cancer and second primary malignan-cies. Stockholm Breast Cancer Study Group [see comment citations in Medline]. Notes Editor's note' SEER is a set of geographically defined, population-based central tumor registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Each registry annually submits its cases to the NCI on a computer tape. These computer tapes are then edited by the NCI and made available for analysis. Curtis et al. (/) described the incidence of second cancers among 14 358 breast cancer patients reported to the Surveillance, Epidemiology, and End Results (SEER) Program who received adjuvant tamoxifen therapy. They found a significant excess of endometrial cancer in accordance with several previous reports but no excess of stomach and colon cancers as reported from three Scandinavian adjuvant tamoxifen trials. Although the SEER data may provide relevant information on the effects of short-term adjuvant tamoxifen therapy, they appear to be of little value for judging the long-term effects of high cumulative doses of tamoxifen (e.g., the cumulative dose resulting from a 20-mg-daily schedule for 5 years, which now has become the standard treatment for most breast cancer patients). In many studies of second cancer incidence after adjuvant tamoxifen therapy, there appears to be a direct relationship between the cumulative dose of tamoxifen and the relative risk of endometrial cancer. In the Stockholm trial, with an average cumulative dose of 42 g, the relative risk was about 6 (2). This excess was similar to that observed in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 trial with a protocol cumulative dose of 37 g (5). In trials using cumulative protocol doses of 11 g, the excess of en-dometrial cancer corresponded to a relative risk on the order of 2-3 (4,5). In the study by Curtis et al. (7), there was no information on the tamoxifen doses actually received by the patients. However, the published figures indicate that the average cumulative dose was low. The ratio between the observed and the expected numbers of endometrial cancer cases among the tamoxifen-treated patients was 2.03. The corresponding ratio for those patients not treated with tamoxifen was 1.23. These figures suggest a relative risk of endo-metrial cancer of less than 2.0 associated with the use of tamoxifen in the SEER material. Given the mentioned results from previous trials, such a low figure …