Abstract P4-08-06: Companion Diagnostic Test for Expression of β-III tubulin (ß3T) in Breast Cancer (BC) Using an Immunohistochemical (IHC) Assay in Studies of Ixabepilone (Ixa)

Autor: C Roach, O. Trifan, R Welcher, P Sève, V Tanna, C Dumontet
Rok vydání: 2010
Předmět:
Zdroj: Cancer Research. 70:P4-08
ISSN: 1538-7445
0008-5472
DOI: 10.1158/0008-5472.sabcs10-p4-08-06
Popis: Background: Preclinical and retrospective clinical data suggest that ≥3T is a biomarker for poor prognosis and resistance to paclitaxel in breast cancer (BC). Preclinical studies have demonstrated that Ixa has activity in ≥3T over-expressing xenograft models resistant to taxanes and Ixa has shown clinical activity in BC patients with high ≥3T mRNA levels [Horak et al., J Clin Oncol 27:15s, 2009 (suppl; abstr 3587]. Dako and BMS have developed an IHC assay for detection of ≥3T to explore the potential of ≥3T as a biomarker to select BC patients that may benefit from Ixa. A neoadjuvant BC study comparing ixa to weekly paclitaxel employs this assay to assess ≥3T expression levels in patients’ tumor samples. Here we describe the application and initial validation testing of the assay in BC tumor samples. Methods: An IHC assay employing a murine monoclonal anti-≥3T antibody (TUJ1) was developed to assess ≥3T expression in formalin-fixed paraffin-embedded tissue specimens. Banked specimens for initial testing included 233 cases of invasive BC. Results: Patterns of ≥3T staining were typically homogeneous cytoplasmic staining with normal tissue elements such as endothelial cells and nerve cells serving as internal positive controls. Staining intensity was scored as 0, 1+, 2+ or 3+ with 0 being no visible staining and 2+ being equal to that of the internal positive control. Tumors with ≥50% cells staining ≥2+ were defined as positive for ≥3T based on previous published studies. Of the 233 breast tumors, 81 (35%) were positive and 152 (65%) were negative for ≥3T expression. HER2 status was defined for 128 of these specimens, with 37 of them (29%) found to be HER2 positive. Comparison of the samples with defined HER2 status demonstrated similar patterns of ≥3T expression, with 15 (40.5%) of the HER2+ samples being positive for ≥3T and 31 (34.1%) of HER2- specimens expressing elevated levels of ≥3T. In pathologist training exercises the inter-reader and intra-reader agreement of ≥3T scoring exceeded 85%. Antigen stability has been confirmed and other assay validation efforts are ongoing. Conclusions: These findings are consistent with previously reported data on ≥3T expression in breast cancer, and support the use of this ≥3T IHC assay in studies with ixabepilone. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-06.
Databáze: OpenAIRE
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