Preliminary Report: Concordance of Community Vs

November 5, 2001

Preliminary Report: Concordance of Community vs. Central HER2 Testing In the Breast Intergroup Study N9831

Patrick C. Roche, PhD Edith A. Perez, MD

1 November 5, 2001

The efficacy of trastuzumab in the metastatic setting coupled with the relatively poor prognosis of patients with node-positive, HER2 positive breast cancer has led to its evaluation in the adjuvant setting. N9831, a prospective randomized three-arm phase III trial led by Edith A. Perez, M.D., is being conducted by all members of the Breast

Intergroup (Cancer and Leukemia Group B, Eastern Cooperative Oncology Group,

Southwestern Oncology Group, and the North Central Cancer Treatment group

(NCCTG), with the NCCTG as the coordinating center1 (http://cancertrials.nci.nih.gov trial #NCIG01-1978). Women with primary, operable, histologically confirmed node positive breast carcinoma that strongly overexpresses HER2 protein, or displays HER2 gene amplification are eligible for this trial. Measurement of HER2 protein may be performed by the FDA-approved DAKO HercepTest (3+ score)2 or another immunohistochemical assay where one third or more of invasive tumor cells stain positive. Gene amplification assays using fluorescence in-situ hybridization (FISH) may be performed by Vysis PathVysion (> 2.0 HER2 probe/control probe ratio considered amplified)3 or Ventana INFORM Her2/neu (5> gene copies of HER2 considered amplified)4. Women whose tumors stain 0, 1+,.or 2+ by community-based immunohistochemistry (IHC), but demonstrate amplification by community-based FISH are eligible for the study.

When central testing for HER2 status has been performed on 119 specimens, only 75% of locally tested tumor specimens are HER2 overexpressed and only 66% are HER2 gene amplified. Only six of the nine (67%) tumors reported to be HER2 gene amplified by community FISH have been found to be HER2 gene amplified by central FISH.

2 November 5, 2001

Eligibility criteria for study entry to this clinical trial has been modified based on these laboratory findings.

3 November 5, 2001

References

1. Perez EA, Comis RL, Kaufman PA, Martino S. Phase III randomized study

of doxorubicin plus cyclophosphamide followed by paclitaxel with or without

trastuzumab (Herceptin) in patients with HER-2-overexpressing breast cancer.

http://cancernet.nci.nih.gov.

2. DAKO HercepTest, DAKO Corp., Carpinteria, CA.

3. PathVysion, Vysis, Inc., Downers Grove, IL

4. INFORM Her-2/neu, Ventana Medical Systems, Inc., Tuscon, AZ.