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

Int J Gynecol Pathol. 1999 Oct;18(4):387-91. doi: 10.1097/00004347-199910000-00015.


Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in 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-erbB2/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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / drug therapy*
  • Carcinoma / enzymology
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • DNA Mutational Analysis
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Female
  • Genes, ras / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Neoplasms, Second Primary / enzymology
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / metabolism
  • Neoplasms, Second Primary / pathology*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Tamoxifen / therapeutic use*


  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)