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

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  • Conway, Kathleen
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Gillings School of Global Public Health, Department of Epidemiology
  • Parrish, Eloise
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Edmiston, Sharon N
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Tolbert, Dawn
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Tse, Chiu-Kit
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Geradts, Joseph
    • Other Affiliation: Department of Pathology, Duke University Medical Center, Durham, NC, USA
  • Livasy, Chad
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Singh, Harsharan
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Newman, Beth
    • Other Affiliation: School of Public Health, Queensland University of Technology, Brisbane, Australia
  • Millikan, Robert C.
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Abstract Introduction Evidence suggests that alterations in estrogen signaling pathways, including estrogen receptor-α (ER-α), occur during breast cancer development. A point mutation in ER-α (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-α A908G mutation by using single-strand conformational polymorphism (SSCP) analysis and 33P-cycle sequencing. Results We detected the ER-α 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-α allele had been lost. The ER-α 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-α 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.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Kathleen Conway et al.; licensee BioMed Central Ltd.
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Journal title
  • Breast Cancer Research
Journal volume
  • 7
Journal issue
  • 6
Page start
  • R871
Page end
  • R880
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1465-5411
Bibliographic citation
  • Breast Cancer Research. 2005 Sep 06;7(6):R871-R880
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • September 5, 2012

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