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Evaluation of Genomic Instability as an Early Event in the Progression of Breast Cancer

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Annual summary rept. 1 Apr 2005-31 Mar 2006

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We have shown in retrospective studies that loss of telomere content TC has potential value in predicting clinical outcome in breast cancer. However, an alternative marker for TC, which could be assessed in samples with small numbers of cells, such as fine needle aspirates, with commonly used methods is desirable. The aim of this study is to demonstrate that measurement of allelic imbalance AI, which could be easily adapted to the clinical laboratory setting, can serve as a surrogate for TC, discriminating between women in need of more aggressive treatment and those for whom aggressive protocols are unnecessary. The candidate has developed a robust assay to determine the extent of AI that discriminates between normal and tumor specimens with 67 sensitivity and 99 specificity. Currently, the candidate is assessing the potential prognostic capabilities of the assay in node negative breast tumors. Additionally, the candidate has shown that increased AI and altered TC are present in both tumors and surrounding histologically normal breast tissues at distances at least one 1cm from the visible tumor margins and decrease as a function of distance. In addition to evaluating a potential biomarker of breast cancer progression, the proposed investigation has provided the candidate opportunities to interact with pathologists and oncologists to learn normal and abnormal breast morphology, the strengths and limitations of currently used breast cancer biomarkers and the scientific rationale for ongoing clinical trials. To date, all tasks, as outlined in the Statement of Work, are on schedule.

Subject Categories:

  • Biochemistry
  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology

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