title: Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer.
abstract: BACKGROUND
  In breast cancer patients, about two thirds of the tumors are estrogen receptor (ER)-positive and one third are ER-negative. The molecular mechanisms leading to the ER-negative phenotype are poorly understood. Nearly all ER-negative and about 40% of ER-positive cancers are resistant to endocrine therapy.
  
  
  OBJECTIVE
  In this study, we examined the entire coding region of the ER gene in ER-positive and ER-negative primary breast tumors to determine whether deletions/insertions or point mutations might account for the ER-negative phenotype.
  
  
  METHODS
  We amplified exons 1 through 8 of the ER gene in 118 ER-positive and 70 ER-negative primary breast tumors and searched for mutations by single-strand conformation polymorphism analysis, denaturing gradient gel electrophoresis, and DNA sequencing.
  
  
  RESULTS
  Both ER-negative and ER-positive tumors contained neutral polymorphisms in codons 10 [TCT-->TCC (Ser)], 87 [GCG-->GCC (Ala)], 243 [CGC-->CGT (Arg)], 325 [CCC-->CCG (Pro)], and 594 [ACA-->ACG (Thr)]. There was no correlation of any of the polymorphic alleles with the ER phenotype or other clinicopathologic parameters including tumor type, size, grade, or stage. However, the polymorphism in codon 325 showed a strong association with a family history of breast cancer (P = .0005). This association was observed both in premenopausal and postmenopausal patients. Despite extensive searching in exons 1 through 8, we found no deletions/insertions and only two missense mutations in codons 69 [AAC (Asn)-->AAG (Lys)] and 396 [ATG (Met)-->GTG (Val)] of the same ER-negative tumor. Thus, only 1% of the primary breast cancers had point mutations in the ER gene.
  
  
  CONCLUSIONS
  In the majority of primary breast cancers, the ER-negative phenotype is not the result of mutations in the coding region of the ER gene, but is due to deficient ER expression at the transcriptional or post-transcriptional level.
  
  
  CONCLUSIONS
  The correlation reported previously, as well as our current findings, suggest that further investigations are warranted to understand the possible linkage of the ER gene locus to hereditary breast cancer.
authors.affiliation: Department of Pathology, Vanderbilt University, Nashville, TN 37232.
authors.forename: N
authors.initials: N
authors.lastname: Roodi
authors.forename: L R
authors.initials: LR
authors.lastname: Bailey
authors.forename: W Y
authors.initials: WY
authors.lastname: Kao
authors.forename: C S
authors.initials: CS
authors.lastname: Verrier
authors.forename: C J
authors.initials: CJ
authors.lastname: Yee
authors.forename: W D
authors.initials: WD
authors.lastname: Dupont
authors.forename: F F
authors.initials: FF
authors.lastname: Parl
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen