%0 Journal Article
%T The estrogen receptor-¦Á A908G (K303R) mutation occurs at a low frequency in invasive breast tumors: results from a population-based study
%A Kathleen Conway
%A Eloise Parrish
%A Sharon N Edmiston
%A Dawn Tolbert
%A Chiu-Kit Tse
%A Joseph Geradts
%A Chad A Livasy
%A Harsharan Singh
%A Beth Newman
%A Robert C Millikan
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr1315
%X 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-¦Á A908G mutation by using single-strand conformational polymorphism (SSCP) analysis and 33P-cycle sequencing.We detected the ER-¦Á 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-¦Á allele had been lost. The ER-¦Á 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.This population-based study, the largest so far to screen for the ER-¦Á 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.The principal risk factors for breast cancer are hormonal or reproductive factors that increase exposure to estrogen [1]. The importance of estrogen in breast cancer development is further supported by studies demonstrating the occurrence of marked changes in estrogen signaling and expression of the two estrogen receptors (ERs) ER-¦Á and ER-¦Â during breast tumorigenesis and progression [2-8]. Although mutations in the ER-¦Á gene are relatively rare in primary breast cancers [2,3], Fuqua and colleagues recently described a point mutation in ER-¦Á in one-third of typical breast hyperplasias [9], and also observed this mutation in a high percentage of breast tumors [10]. This A¡úG base substitution at nucleotide 908 in codon 303, referred to
%U http://breast-cancer-research.com/content/7/6/R871