Systematic Review: Gene Expression Profiling Assays in Early-Stage Breast Cancer

4 March 2008 | Volume 148 Issue 5

Background: Three gene expression–based prognostic breast cancer tests have been licensed for use.

Purpose: To summarize evidence on the validity and utility of 3 gene expression–based prognostic breast cancer tests: Oncotype DX (Genomic Health, Redwood City, California), MammaPrint (Agendia BV, Amsterdam, the Netherlands), and H/I (AvariaDX, Carlsbad, California).

Data Sources: MEDLINE, EMBASE, and Cochrane databases (from 1990 through January 2007), Web sites of the test manufacturer, and discussion with the manufacturers.

Study Selection: Original data studies published in English that addressed prognostic accuracy and discrimination or treatment benefit prediction of any of the 3 tests in women with breast cancer.

Data Extraction: Information was extracted about the clinical characteristics of the study population (particularly clinical and therapeutic homogeneity), tumor characteristics, and whether the marketed test or underlying signature was evaluated.

Data Synthesis: The tests are based on distinct gene lists, using 2 different technologies. Overall, the body of evidence showed that this new generation of tests may improve prognostic and therapeutic prediction, but the tests are at different stages of development. Evidence shows that the tests offer clinically relevant, improved risk stratification over standard predictors. Oncotype DX has the strongest evidence, closely followed by MammaPrint and the H/I test (which is still maturing).

Limitations: For all tests, the relationship of predicted–observed risk in different populations needs further study, in addition to their incremental contribution over conventional predictors, optimal implementation, and relevance to patients receiving current therapies.

Conclusion: Gene expression technologies show great promise to improve predictions of prognosis and treatment benefit for women with early-stage breast cancer. More information is needed on the extent of improvement in prediction, in whom the tests should be used, and how test results are best incorporated into decision making about breast cancer treatment.

Author and Article Information

From Johns Hopkins University, School of Medicine, Baltimore, Maryland.

Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Grant Support: This project was funded under contract no. 290-02-0018 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.

Requests for Single Reprints: Steven N. Goodman, MD, MHS, PhD, Johns Hopkins University, School of Medicine, 550 Building, Room 11-03, Baltimore, MD 21205; e-mail, sgoodman{at}jhmi.edu.

Current Author Addresses: Drs. Marchionni and Wolff: Johns Hopkins University, School of Medicine, Oncology Cancer Biology, Baltimore, MD 21287.

Ms. Wilson, Dr. Marinopoulos, and Dr. Bass: Johns Hopkins University, School of Medicine, General Internal Medicine, Baltimore, MD 21287.

Dr. Parmigiani: Johns Hopkins University, School of Medicine, Oncology Informatics, Baltimore, MD 21287

Dr. Goodman: Johns Hopkins University, School of Medicine, Oncology Biostatistics, Baltimore, MD 21287.

Read all Rapid Responses

Letter to the Editor

Lawrence C. Panasci, et al.

Annals Online, 18 Mar 2008 [Full text]

Reaction to Systematic Review: Gene Expression Profiling Assays in Early-Stage Breast Cancer

Rene Bernards, et al.

Annals Online, 5 May 2008 [Full text]

Author's response to letter from Bernard

Steven N. Goodman, et al.

Annals Online, 9 Jun 2008 [Full text]