The estrogen receptor-alpha A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study.

Journal Article (Journal Article)

INTRODUCTION: Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor-alpha (ER-alpha), occur during breast cancer development. A point mutation in ER-alpha (nucleotide A908G), producing an amino acid change from lysine to arginine at codon 303 (K303R) results in receptor hypersensitivity to estrogen. This mutation was initially reported in one-third of hyperplastic benign breast lesions, although several recent studies failed to detect it in benign or malignant breast tissues. METHODS: We screened 653 microdissected, newly diagnosed invasive breast tumors from patients in the Carolina Breast Cancer Study, a population-based case-control study of breast cancer in African American and white women in North Carolina, for the presence of the ER-alpha A908G mutation by using single-strand conformational polymorphism (SSCP) analysis and 33P-cycle sequencing. RESULTS: We detected the ER-alpha A908G mutation in 37 of 653 (5.7%) breast tumors. The absence of this mutation in germline DNA confirmed it to be somatic. Three tumors exhibited only the mutant G base at nucleotide 908 on sequencing, indicating that the wild-type ER-alpha allele had been lost. The ER-alpha A908G mutation was found more frequently in higher-grade breast tumors (odds ratio (OR) 2.83; 95% confidence interval (CI) 1.09 to 7.34, grade II compared with grade I), and in mixed lobular/ductal tumors (OR 2.10; 95% CI 0.86 to 5.12) compared with ductal carcinomas, although the latter finding was not statistically significant. CONCLUSION: This population-based study, the largest so far to screen for the ER-alpha A908G mutation in breast cancer, confirms the presence of the mutant in invasive breast tumors. The mutation was associated with higher tumor grade and mixed lobular/ductal breast tumor histology.

Full Text

Duke Authors

Cited Authors

  • Conway, K; Parrish, E; Edmiston, SN; Tolbert, D; Tse, C-K; Geradts, J; Livasy, CA; Singh, H; Newman, B; Millikan, RC

Published Date

  • 2005

Published In

Volume / Issue

  • 7 / 6

Start / End Page

  • R871 - R880

PubMed ID

  • 16280033

Pubmed Central ID

  • PMC1410768

Electronic International Standard Serial Number (EISSN)

  • 1465-542X

Digital Object Identifier (DOI)

  • 10.1186/bcr1315


  • eng

Conference Location

  • England