potential flaw in ONCODX test (false negative her2 results) may have been identified

[Lani]

High false-negative rate of HER2 qRT-PCR of the Oncotype DX test: An independent quality assurance study.


Sub-category:
HER2+

Category:
Breast Cancer - HER2/ER

Meeting:
2011 ASCO Annual Meeting

Abstract No:
603

Citation:
J Clin Oncol 29: 2011 (suppl; abstr 603)


Attend this session at the
ASCO Annual Meeting!
Session: Breast Cancer - HER2/ER

Type: General Poster Session

Time: Monday June 6, 1:00 PM to 5:00 PM

Location: McCormick Place Hall A



Author(s): D. J. Dabbs, M. Klein, S. Mohsin, R. R. Tubbs, R. Bhargava; Magee-Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA; Riverside Methodist Hospital, Columbus, OH; Cleveland Clinic Foundation, Cleveland, OH


Abstract Disclosures


Abstract:

Background: HER2 (ERBB2) status is an important prognostic and predictive marker in breast carcinoma. In recent years, Genomic Health, Inc. (GHI), purveyors of the Oncotype DX test, have been separately reporting HER2 by reverse transcription polymerase chain reaction (RT-PCR) to oncologists. Due to lack of independent evaluation, this quality assurance study was undertaken to define the concordance rate between immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and GHI RT-PCR HER2 assay. Methods: All cases at three participating laboratories (MWH-Magee-Womens Hospital, CC-Cleveland Clinic, RMH-Riverside Methodist Hospital) with available HER2 RT-PCR results from GHI were included in this study. All IHC positive and equivocal cases were further evaluated and classified by FISH at respective laboratories. Results: Of the total 507 MWH cases, 236 CC cases, and 100 RMH cases; 99% (464/468) of MWH, 99.5% (221/222) of CC, and 100% (94/94) of RMH negative cases were also negative by GHI RT-PCR assay. However, all MWH (n=13), CC (n=8) and RMH (n=2) equivocal cases were reported as negative by GHI. Of the 26 MWH positive cases, 8 were positive and 18 were either negative or equivocal by GHI (concordance of 31%). Concordance for positive cases was 17% (1 of 6) at CC and 25% (1 of 4) at RMH. Conclusions: There is an unacceptable false-negative rate for HER2 status via Oncotype DX in this independent study. This can create confusion in decision making process for targeted treatment, and can potentially lead to mismanagement of breast cancer patients if only GHI HER2 information is used. The Oncotype DX assay for Her2 has a flawed, inconsistent methodology that is not robust, and this raises serious concern about the validity of the Oncotype DX test.