Please select Print from the file menu or right mouse click and choose print from the menu to print this page.

[109] Expression of a Novel Cell-Cycle Regulated Protein HTF9C, Identifies a Subgroup of HER2 Positive Breast Cancer with a More Aggressive Clinical Course

DC Dim, DG Hicks, BJ Yoder, RR Tubbs, TG Budd, BZ Ring, RA Beck, NC Estopinal, RS Seitz, DT Ross. Roswell Park Cancer Institute, Buffalo, NY; MicroPath Labs, Lakeland, FL; Cleveland Clinic Foundation, Cleveland, OH; Applied Genomic Inc, Burlingame, CA; Comprehensive Institute of Huntsville, Huntsville, AL

Background: Over-expression of HER2 in a subset of breast cancers (HER2+) is associated with higher grade tumors that are clinically more aggressive. Despite these distinctive clinical features, significant heterogeneity exists among patients with HER2+ disease with roughly half of these tumors expressing hormone receptors, as well as demonstrating varying degrees of responsiveness to Trastuzumab therapy. The identification of factors that may help better define the clinical diversity of HER2+ tumors would likely benefit clinical decision-making and suggest new approaches to overcome Trastuzumab resistance.
Design: Tissue microarrays from two established breast cancer cohorts (CCIH CCF, J Clin Oncol 24:3039-47,2006) were used to investigate potential IHC markers to help stratify HER2+ breast cancer patients into different prognostic categories. 37 Antibodies were selected based on their ability to reproducibly divide the HER2+ patients into two independent subgroups. The CCIH cohort was used to identify the subset of markers with a univariate association of IHC staining with clinical outcome and these associations were tested on the CCF cohort.
Results: An antibody to HTF9C showed strong correlation with likelihood of recurrence at 5 years within 67 HER2+ patients from the CCIH cohort (HR 4.80; 95% CI 1.77 to 13.10, p < 0.002). The sensitivity and specificity were 50% 87%. This prognostic correlation was validated on 75 HER2+ patients from the CCF cohort (HR 3.63; 95% CI 1.26 to 10.50, p < 0.02). The sensitivity and specificity were 60% 70%. When the two cohorts are combined in silico, the sensitivity and specificity were 55% 79%.
Conclusions: HTF9C, a novel, cell-cycle regulated, protein is differentially expressed across tumors (Mol Biol Cell 13:1977-2000,2002) and correlates with poor prognosis in ER+ positive breast cancer and lung cancer. Here we show that in two independent cohorts, it correlates with poor prognosis in HER2+ patients. As these patients were not treated with Trastuzumab before the recurrence event, it is of great interest to see how HTF9C correlates with prognosis in a HER2+ population treated adjuvantly with Trastuzumab.
Category: Breast

Monday, March 26, 2007 1:15 PM

Platform Session: Section D, Monday Afternoon