Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer.
Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer.
- 2014
Available online from the MWHC library: 1948 - present, Available in print through MWHC library: 1999 - 2006
BACKGROUND: The importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options. CONCLUSIONS: This study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a single test to rule out potential benefit from HER2-targeted therapy. 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. METHODS: Breast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared. RESULTS: Of the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were determined to be HER2-positive (95% confidence interval [CI]=2.5%-5.7%). Of these, 18 had been tested locally by only one testing methodology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95% CI=3.8-15.9 months] versus 9.1 months [95% CI=8.3-10.3 months]) and overall survival (25.9 months [95% CI=13.8-not estimable] versus 27.9 months [95% CI=25.0-32.9 months]).
English
0008-543X
*Breast Neoplasms/me [Metabolism]
*Receptor, erbB-2/me [Metabolism]
*Tumor Markers, Biological/me [Metabolism]
Breast Neoplasms/di [Diagnosis]
Breast Neoplasms/ge [Genetics]
False Negative Reactions
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Middle Aged
Prospective Studies
Receptor, erbB-2/ge [Genetics]
Sensitivity and Specificity
Tumor Markers, Biological/ge [Genetics]
Washington Cancer Institute
Comparative Study
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Available online from the MWHC library: 1948 - present, Available in print through MWHC library: 1999 - 2006
BACKGROUND: The importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options. CONCLUSIONS: This study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a single test to rule out potential benefit from HER2-targeted therapy. 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. METHODS: Breast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared. RESULTS: Of the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were determined to be HER2-positive (95% confidence interval [CI]=2.5%-5.7%). Of these, 18 had been tested locally by only one testing methodology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95% CI=3.8-15.9 months] versus 9.1 months [95% CI=8.3-10.3 months]) and overall survival (25.9 months [95% CI=13.8-not estimable] versus 27.9 months [95% CI=25.0-32.9 months]).
English
0008-543X
*Breast Neoplasms/me [Metabolism]
*Receptor, erbB-2/me [Metabolism]
*Tumor Markers, Biological/me [Metabolism]
Breast Neoplasms/di [Diagnosis]
Breast Neoplasms/ge [Genetics]
False Negative Reactions
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Middle Aged
Prospective Studies
Receptor, erbB-2/ge [Genetics]
Sensitivity and Specificity
Tumor Markers, Biological/ge [Genetics]
Washington Cancer Institute
Comparative Study
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't