Diagnostic Utility of a 92-Gene Classifier in Triple-Negative Breast Carcinomas
Elena F Brachtel, Sarah E Kerr, Jeff Anderson, Yi Zhang, Veena Singh, Mark G Erlander, Brittany Carey, W Edward Highsmith, Catherine A Schnabel, Sarah M Dry, Peggy S Sullivan. Massachusetts General Hospital and Harvard Medical School, Boston, MA; Mayo Clinic, Rochester, MN; bioTheranostics, Inc., San Diego, CA; University of California Medical Center, Los Angeles, CA
Background: Triple-negative breast carcinomas (TNBCs) are often poorly differentiated and can present as metastases of unknown origin since they are commonly negative for most immunohistochemical breast markers. Accurate and timely diagnosis of TNBC, which accounts for 10% to 20% of all breast cancers, is critical for appropriate treatment and participation in clinical trials. A recent multi-institutional validation study of a 92-gene molecular cancer classifier showed 87% accuracy (n=790) to predict tumor origin of 28 tumor types. In this subgroup analysis, performance of the 92-gene assay in the classification of TNBCs was further examined.
Design: Formalin fixed paraffin embedded tumor samples were selected after a 3-pathologist-adjudicated review using whole slide imaging technology and ancillary clinical information. Samples were tested in a blinded fashion using the CancerTypeID® 92-gene classifier (bioTheranostics, Inc), which makes tumor type predictions based upon gene expression profiling of 87 gene targets and 5 reference genes by quantitative reverse transcriptase PCR; molecular results reported as rank probabilities were compared to the pathological diagnosis.
Results: The current analysis included 34 breast cancers (65% metastatic) from female patients. 77% (23/30) were high grade, 20% (6/30) grade 2/3, and 3% (1/30) grade 1/3. 4 cases could not be graded. 21% (7/33) were ER-HER2- or TNBCs, 40% (13/33) ER+HER2-, 21% (7/33) ER-HER2+ and 18% (6/33) ER+HER2+. 1 case was without receptor/HER2 status. Overall, 74% (25/34 cases) were correctly classified as breast origin by the 92-gene classifier in this study. 86% of TNBCs (6/7) and 79% of ER+ breast cancers (15/19) were correctly classified as breast origin. 7 incorrectly classified cases, mostly HER2+, were identified as salivary gland origin. One case was unclassifiable.
|TNBC (%)||ER+HER2- (%)||ER-HER2+ (%)||ER+HER2+ (%)|
|Breast Cancer Cases N=33||7 (21)||13 (40)||7 (21)||6 (18)|
|92-Gene Classifier Prediction Breast||6 (86)||11 (85)||3 (43)||4 (67)|