The Influence of BRCA1 and BRCA2 Mutations on Prognosis in Breast Cancer Occuring in Ashkenazi Women: A Historical Cohort Approach

Abstract

Using a historical approach, we studied the clinicopathological features of hereditary breast cancer (BC) and related this to the outcome following the BC diagnosis. We ascertained all self-reporting Ashkenazi Jewish (AJ) women diagnosed with primary invasive BC from 1980 to 1995. Diagnostic, treatment and follow-up information was extracted from the medical chart and the pathology blocks (PB) were re-examined by one pathologist. Slides were prepared for immunohistochemistry (IHC) and DNA extracted from the PB was used to look for the recurrent Ad mutations L85DELAG, 53S2insC (BRCAl) and 6174de1T (BRGA2) j . Of the 202 PB, 32 carried a mutation in BRCAl (24) or BRCA2 (8) . BRCAl was associated with high grade, ER- BC (P <.001). BRCA2+ BC were usually ER+. Neither ERCAl nor BRCA2 were correlated with tumor size. BRCAl/2+ status was also correlated with p53 over- expression and p27 (kipl) under-expression by IHC, but not with HER2 status. A positive BRCAlX2 status was an independent poor prognostic marker in BC. In conclusion, ER CAl /2 mutations confer a specific phenotype on the BC that occur and when combined, are an independent adverse prognostic marker for breast cancer in Ad women. Larger studies in other populations will be required to confirm our findings.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2000
Accession Number
ADA389641

Entities

People

  • William David Foulkes

Organizations

  • McGill University

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DTIC Thesaurus Topics

  • Breast Cancer
  • Chemical Synthesis
  • Chemistry
  • Databases
  • Genetics
  • Health Services
  • Medical Genetics
  • Medical Personnel
  • Oncology
  • Physicians
  • Proteins

Fields of Study

  • Biology
  • Medicine

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  • Molecular and genetic basis of cancer.
  • Oncology and Biomarker-Based Cancer Detection.
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