Endometrial carcinoma in tamoxifen-treated breast cancer patient: Clinicopathological, immunohistochemical, and genetic analysis

Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcino ma that developed in a woman receiving low-dose tamoxifen treatment for bre ast cancer. Little is known about steroid receptor status, somatic alterati ons in oncogenes and tumor suppressor genes, and inherited susceptibility i n endometrial carcinomas associated with tamoxifen use. In the present case , the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB 2/neu, cyclin D1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene, The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in DNA methylation.