Abstract P6-05-03: Analysis of College of American Pathologists Recommendations for Reporting HER2 Intra-Tumoral heterogeneity (ITH) on 1329 Breast Cancers

Abstract

Background: The College of American Pathologists (CAP) recently published recommendations for reporting intratumoral heterogeneity for HER2 gene amplification in breast cancers. These guidelines recommend reporting cases with between 5-50% of cells with HER2:CEP17 ratios > 2.2 (or > 6 HER2 signals/cell) as “heterogeneous for HER2 gene amplification.” Because these recommendations lack biological and clinical foundation, we applied them to a large number of historical breast cancers and compared the ITH classification to routine FISH Her2 results. Materials and Methods: We collected Her2 and CEP17 counts in 32,116 tumor cells from 1329 consecutive breast cancer cases analyzed by FISH. Data from Excel counting sheets were imported to a SQL Server database for analysis and statistics; histograms and analyses were also performed in Excel. We specifically computed concordances between guidelines for traditional and intra-tumoral heterogeneity (ITH) reporting. Results: 309 of 1,329 cases (23%) met the criteria for heterogeneous HER2 gene amplification by HER2:CEP17 ratio, but > 79% of these were non-amplified by standard FISH reporting criteria. Using Her2 signals per cell, ITH was found in 87 (6.5%) of cases and most of these were not amplified or equivocal by standard criteria. Discussion: A significant proportion of breast cancers contain ITC heterogeneity based on CAP/ASCO reporting recommendations. The majority of these cases are non-amplified without consideration of ITH. Because it is not known whether these patients (who would not currently be treated) would benefit from HER2 targeted therapies, it may be premature to use the ITH reporting recommendations for clinical decision-making. More validation of ITH criteria and biological significance are needed. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-03.