Skip Navigation Archive: U.S. Department of Health and Human Services U.S. Department of Health and Human Services
Archive: Agency for Healthcare Research Quality
Archival print banner

This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: Let us know the nature of the problem, the Web address of what you want, and your contact information.

Please go to for current information.

Breast Tumors, HER2 Testing

Structured Abstract
Full Title: HER2 Testing to Manage Patients with Breast or Other Solid

Objectives: Systematic review of trastuzumab outcomes among breast cancer patients who have negative, equivocal, or discordant HER2 assay results; use of HER2 assay results to predict outcomes of chemotherapy or hormonal therapy regimen for breast cancer; use of serum HER2 to monitor treatment response or disease progression in breast cancer patients; and use of HER2 testing to manage patients with lung, ovarian, prostate, or head and neck tumors. Also, narrative review of concordance of HER2 assays.

Data Sources: We abstracted data from: three articles plus one conference abstract on negative, equivocal, or discordant HER2 results; 26 studies on selection of chemotherapy or hormonal therapy; 15 studies on serum HER2; and 26 studies on ovarian, lung, prostate, or head and neck tumors. Foreign-language studies were included.

Review Methods: We sought randomized trials or single-arm series (prospective or retrospective) of identically treated patients that presented relevant outcome data associated with HER2 status.

Results: HER2 assay results are influenced by multiple biologic, technical, and performance factors. Many aspects of HER2 assays were standardized only recently, so inconsistencies confound the literature comparing different methods. The evidence is weak on outcomes of trastuzumab added to chemotherapy for HER2-equivocal, -discordant, or -negative patients. Evidence comparing chemotherapy outcomes in HER2-positive and HER2-negative patient subgroups may generate hypotheses, but is too weak to test hypotheses. Only a rigorous test can resolve whether HER2-positive patients (but not HER2-negative patients) benefit from an anthracycline regimen. Evidence is available only from uncontrolled series on whether HER2 status predicts complete pathologic response to neoadjuvant chemotherapy.

Evidence also is weak regarding differences by HER2 status for outcomes of chemotherapy for advanced or metastatic disease; with most studies lacking statistical power. Data from studies of tamoxifen and aromatase inhibitors suggest that future studies should examine whether HER2 status predicts response to specific hormonal therapies among estrogen-receptor-positive patients.

The evidence is weak on whether serum HER2 predicts outcome after treatment with any regimens in any setting, as is the evidence on use of serum or tissue HER2 testing for malignancies of lung, ovary, head and neck, or prostate.

Conclusions: Overall, few studies directly investigated the key questions of this systematic review. Going forward, cancer therapy trial protocols should incorporate elements to facilitate robust analyses of the use of HER2 status and other biomarkers for managing treatment. 

Download Report

HER2 Testing to Manage Patients with Breast or Other Solid Tumors

Evidence-based Practice Center: Blue Cross and Blue Shield Association
Topic Nominators: American Association for Clinical Chemistry

Page last reviewed October 2014
Page originally created November 2008
Internet Citation: Breast Tumors, HER2 Testing. Content last reviewed October 2014. Agency for Healthcare Research and Quality, Rockville, MD.


The information on this page is archived and provided for reference purposes only.


AHRQ Advancing Excellence in Health Care