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Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after treatment. Most women with Stage I or II node-negative breast cancer (especially when estrogen-receptor positive and treated with tamoxifen) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to benefit from chemotherapy. Several clinically available gene expression profiles (GEP) provide “recurrence risk scores” that are intended to supplement information used by clinicians and patients in treatment decision-making.
Tumor gene expression profiling in women with Stage I or II node-negative breast cancer to predict recurrence risk and guide decisions about chemotherapy.
Reverse transcription PCR is used by Oncotype DX and the H:I Ratio Test (Breast cancer Gene Expression Ratio Assay) for the detection and quantification of mRNA in formalin fixed, paraffin-embedded breast cancer tissue. Oncotype DX analyzes the expression of 21 genes (16 cancer related and 5 normative). The H:I Ratio Test measures the ratio of the expression of the homeobox gene-B13 (HOXB13) and the interleukin-17B receptor gene (IL17BR). MammaPrint uses micro-array technology to test for 70 cancer related and about 1800 normative genes in unfixed (fresh or frozen) breast cancer tissue.  
Breast cancer is the most commonly diagnosed cancer in U.S. women with an estimated 207,090 new cases in 2010. Among U.S. women, it is the second leading cause of cancer-related deaths (estimated 39,840 deaths in 2010). Stage I/II accounts for over 50% of all diagnoses, and is associated with a 5 year survival rate of 98%. Among women with early stage node-negative disease, the majority elect to receive chemotherapy on the basis of standard recurrence risk classification using tumor characteristics.  Approximately 60%, 5%, and 0.5% of women respectively will experience minor, major or fatal toxicity from chemotherapy.   Studies of use of breast cancer GEP suggest changes in treatment decisions in approximately 25-30% of cases, most commonly selection of endocrine therapy alone due to reclassification of women from high to low-risk of recurrence .  If tumor gene expression profiles are conclusively shown to result in more accurate classification of women into low and high recurrence risk categories, theoretical benefits would include avoidance of unnecessary chemotherapy and reduced disease recurrence rates.
Systematic evidence reviews
Recommendations by independent group*
Available data have been systematically reviewed and evaluated, providing the basis for a recommendation statement: “The Evaluation of Genomics in Practice and Prevention (EGAPP) Working Group found insufficient evidence to make a recommendation for or against the use of tumor gene expression profiles to improve outcomes in defined populations of women with breast cancer.”
Guidelines by professional groups
* independent groups include the US Preventive Services Task Force (USPSTF) and Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.
Test accuracy and reliability in measuring differences in expression of relevant genes (analytic sensitivity and specificity).
Clinical Validity:Test accuracy and reliability in predicting breast cancer recurrence and benefit from chemotherapy (predictive value).
Clinical Utility: Net benefit of test in improving health outcomes.
For recent additions to the literature, see PubMed special query (2007-present).
Last updated: June 8, 2010