Value Addition: TargetPrint

TargetPrint®Provides Quantification of ER, PR and HER2 Status


TargetPrint is a microarray-based gene expression test which offers a quantitative assessment of the patient’s level of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu overexpression within her breast cancer. TargetPrint is offered in conjunction with MammaPrint to provide the physician an even more complete basis for treatment decisions. 

 

As compared to Immunohistochemistry (IHC), TargetPrint delivers an added benefit to the diagnostic process. IHC provides a semi-quantitative positive or negative result, whereas the gene expression result provided by TargetPrint allows physicians to integrate the absolute level of ER, PR and HER2 gene expression into treatment planning.

ER, PR and HER2 read-outs are determined by measuring the level of gene expression for the three biomarkers. The single read-out is performed on quality-controlled DNA microarrays in Agendia’s state-of-the-art CLIA (Clinical Laboratory Improvement Act) and CAP (College of American Pathologists) registered and compliant genomics laboratories in Irvine, California and Amsterdam, The Netherlands.

 

TargetPrint®Validation

 

TargetPrint has been validated on over 500 breast cancer tumor samples from three independent studies. Validation was achieved using Immunohistochemistry tests (IHC) performed at an independent US-based, CLIA and CAP accredited national reference laboratory for comparison. 

 

The Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 microarray values were compared to the IHC results which were assessed at one central laboratory, yielding a 93% concordance (95CI: 91-95%) for ER, an 83% concordance (95CI: 80-86%) for PR and a 96% concordance (95CI: 94-98%) for HER2, respectively.  For ER and PR, a threshold of 1% IHC positively stained tumor cells was used to classify samples as positive; for HER2, an IHC score of 3+ was considered positive. In the case of 2+ samples, FISH assessed final HER2 amplification status.(13,14) 

 

Results That Support Treatment Decisions

 

TargetPrint®Results for ER/PR

 

TargetPrint provides quantitative measurements that give physicians additional insight into the biology of each individual tumor and assists in treatment decisions. A positive ER measurement predicts a Tamoxifen benefit.(18) The TargetPrint quantitative gene results enable clarification of uncertain or borderline immunohistochemistry results (IHC).

 

TargetPrint Results for HER2

 

Quantitative data about the HER2/neu expression level in an individual tumor can affect the choice of treatment. HER2/neu is important as the target of the monoclonal antibody, trastuzumab (Herceptin®). Trastuzumab is only effective in breast cancer where the HER2/neu receptor is over-expressed.(19) TargetPrint provides physicians and patients with reliable results.

 

Reference

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  2. Oyama T, Ishikawa Y, Hayashi M, Arihiro K, Horiguchi J. The effects of fixation, processing and evaluation criteria on immunohistochemical detection of hormone receptors in breast cancer. Breast Cancer 2007;14:182-8.
  3. Ross JS, Symmans WF, Pusztai L, Hortobagyi GN. Standardizing slide-based assays in breast cancer: hormone receptors, HER2, and sentinel lymph nodes. Clin Cancer Res 2007;13:2831-5.
  4. Kirkegaard T, Edwards J, Tovey S, et al. Observer variation in immunohistochemical analysis of protein expression, time for a change? Histopathology 2006;48:787-94.
  5. Diaz LK, Sahin A, Sneige N. Interobserver agreement for estrogen receptor immunohistochemical analysis in breast cancer: a comparison of manual and computer-assisted scoring methods. Ann Diagn Pathol 2004;8:23-7.
  6. Arihiro K, Umemura S, Kurosumi M, et al. Comparison of evaluations for hormone receptors in breast carcinoma using two manual and three automated immunohistochemical assays. Am J Clin Pathol 2007;127:356-65.
  7. Gancberg D, Järvinen T, di Leo A, et al. Evaluation of HER-2/NEU protein expression in breast cancer by immunohistochemistry: an interlaboratory study assessing the reproducibility of HER-2/NEU testing. Breast Cancer Res Treat 2002;74:113-20.
  8. Allred DC. Commentary: hormone receptor testing in breast cancer: a distress signal from Canada. Oncologist 2008;13:1134-6.
  9. Viale G, Regan MM, Maiorano E, et al. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol 2007;25:3846-52.
  10. Rhodes A, Jasani B, Barnes DM, Bobrow LG, Miller KD. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol 2000;53:125-30.
  11. Perez EA, Suman VJ, Davidson NE, et al. HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 2006;24:3032-8.
  12. Reddy JC, Reimann JD, Anderson SM, Klein PM. Concordance between central and local laboratory HER2 testing from a community-based clinical study. Clin Breast Cancer 2006;7:153-7.
  13. Ach et al., 2007, Robust inter-laboratory reproducibility of a gene-expression signature measurement consistent with the needs of a new generation of diagnostic tools. BMC Genomics 8; 148
  14. Glas et al., 2006, Converting a breast cancer microarray signature into a high-throughput diagnostic test, BMC Genomics, 7:278
  15. Roepman et al., 2008, Microarray based read-out of ER, PR and HER2 expression in breast cancer tissue, abstract, abstract ASCO Breast Conference 2008
  16. Bueno-de-Mesquita et al, 2007, Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER), Lancet Oncology, 2007 Dec;8(12):1079-87
  17. van de Vijver et al, 2002, A gene-expression signature as a predictor of survival in breast cancer, New England Journal of Medicine, Dec 19;347(25)
  18. EBCTCG, Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet 365;1687-1717
  19. Ross et al. (2003) The Her-2/neu gene and protein in breast cancer: biomarker and target of therapy. Oncologist 8 (4): 307-25

 

Information extracted from Agendia.com