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    Research Grants Awarded

    Early detection of high-risk patients with breast DCIS

    Study Section:
    Detection, Diagnosis and Prognosis

    Scientific Abstract:
    a. Background: One of the most important aspects of the management of high-risk patients with localized breast ductal carcinoma in situ (DCIS) is their early identification, prior to clinically overt appearance of progression to invasive breast cancer, which leads to a life-threatening stage of the disease. However, presently available prognostic markers are ineffective to identifying the high-risk patients in this group. In this context, recent studies have shown that the expression of Her-2.neu or an inducible isoform of cyclooxygenase (COX-2) are significantly associated with poor prognosis of patients with primary invasive breast cancer in general or in an estrogen receptor (ER)-positive subgroup, respectively. However, despite the effectiveness of these prognostic markers for patients with primary invasive breast cancer, their individual expression to identify high-risk patients with DCIS remains poorly documented. Therefore, in accordance with one of the Komen Breast Cancer Foundation’s primary objectives (the new research emphasis: DCIS), the determination of frequency of co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER expression in relation to each other, to histologic parameters and to clinical outcome of the disease offers a rationale basis for the early identification of high-risk patients with DCIS. b. Objective/Hypothesis: The co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER are associated with high-risk of progression to invasive breast cancer in patients with DCIS. c. Specific Aim: Retrospective evaluation of association of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER as valuable prognostic markers for high-risk patients with DCIS. d. Study Design: The co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER will be determined in each section of tissue specimen with specific antibodies to these markers by the double-antibody immunohistochemical (IHC) staining method. The sections of archival tissue specimens have been obtained from a well-documented cohort of 310 patients with DCIS. In order to perform multivariate analyses, the following information for each patient is available: age at diagnosis, follow-up after surgery (median follow-up of 8 years), tumor type, margin of the excised lesion, therapy and the clinical outcome of the disease. Of the 310 patients, 67 have developed invasive breast cancer during the course of follow-up. e. Potential outcome and benefits of the research: The aim of the retrospective study, if confirmed, will establish the co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER as valuable and independent prognostic markers for the early identification of high-risk patients with DCIS.

    Lay Abstract:
    a. Background: The currently available prognostic markers have been reported to be ineffective to identifying high-risk patients with localized breast ductal carcinoma in situ (DCIS), prior to clinically overt appearance of progression to invasive breast cancer, which leads to a life-threatening stage of the disease. In this context, expression of one of the most established prognostic markers (Her-2.neu) and an emerging prognostic marker (cyclooxygenase-2, COX-2) for primary invasive breast cancer in general or in a subset of estrogen receptor (ER)-positive breast cancer, respectively, remain poorly documented in terms of their individual prognostic value for patients with DCIS. Therefore, in accordance with one of the Komen Breast Cancer Foundation’s primary objectives (the new research emphasis: DCIS), the determination of frequency of co- expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER offers a rationale basis for the early identification the high-risk patients with DCIS. b. Objective/Hypothesis: The co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER are associated with high-risk of progression to invasive breast cancer in patients with DCIS. c. Specific Aim: Retrospective evaluation of association of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER as valuable prognostic markers for high-risk patients with DCIS. d. Study Design: The co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER will be visualized in DCIS cells by co-probing each section of the tissue specimen with specific antibodies to these markers by a technique called the “double-antibody immunohistochemical staining” method. The sections of archival tissue specimens have been obtained from a well-documented group of 310 patients having DCIS, with known clinical outcome of the disease. The statistical analyses will be performed to determine significant association of expression of the proposed prognostic markers and the outcome of the disease. e. Potential outcome and benefits of the research: The aim of the retrospective study, if confirmed, will establish the co-expression of Her-2.neu and COX-2, Her-2.neu and ER or COX-2 and ER as valuable and independent prognostic markers for the early identification of high-risk patients with DCIS.