Can tumor gene expression profiling improve outcomes in patients with breast cancer?

The expression of specific genes within breast tumor cells has been found to be associated with the chance of disease recurrence. Several gene expression profiles (GEP) are clinically available that provide variations on “recurrence risk scores” intended to help doctors and their patients in treatment decision-making. Determination of breast cancer GEP recurrence risk scores has been proposed as a means to identify those women most likely to benefit from chemotherapy.

EGAPP Recommendation Statement: The 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. For one test, the EWG found preliminary evidence of potential benefit of testing results to some women who face decisions about treatment options (reduced adverse events due to low risk women avoiding chemotherapy), but could not rule out the potential for harm for others (breast cancer recurrence that might have been prevented). The evidence is insufficient to assess the balance of benefits and harms of the proposed uses of the tests. The EWG encourages further development and evaluation of these technologies.

EGAPP Recommendation (January 2009)

Evidence Report (January 2008)

Summary Manuscript (March 2008)

CDC Summary of EGAPP Recommendation (August 2010)

Key Questions:

  • Question 1 (Overarching Question): What is the direct evidence that gene expression profiling tests in women diagnosed with breast cancer (or any specific subset of this population) lead to improvement in outcomes?

  • Question 2: What are the sources of and contributions to analytic validity in these two gene expression-based prognostic estimators for women diagnosed with breast cancer?

  • Question 3: What is the clinical validity of these tests in women diagnosed with breast cancer?

  • Question 3a: How well does this testing predict recurrence rates for breast cancer compared to standard prognostic approaches? Specifically, how much do these tests add to currently known factors or combination indices that predict the probability of breast cancer recurrence, (e.g., tumor type or stage, age, ER, and human epidermal growth factor receptor 2 (HER2) status)?

  • Question 3b: Are there any other factors, which may not be components of standard predictors of recurrence (e.g., race/ethnicity or adjuvant therapy), that affect the clinical validity of these tests, and thereby generalizability of results to different populations?

  • Question 4: What is the clinical utility of these tests?

  • Question 4a: To what degree do the results of these tests predict the response to chemotherapy, and what factors affect the generalizability of that prediction?

  • Question 4b: What are the effects of using these two tests and the subsequent management options on the following outcomes: testing or treatment related psychological harms, testing or treatment related physical harms, disease recurrence, mortality, utilization of adjuvant therapy, and medical costs.

  • Question 4c: What is known about the utilization of gene expression profiling in women diagnosed with breast cancer in the United States?

  • Question 4d: What projections have been made in published analyses about the cost-effectiveness of using gene expression profiling in women diagnosed with breast cancer?


Why EGAPP Selected this Topic for Review:

Key Criteria: Prevalence and severity of breast cancer; relevance to healthcare providers and patients for decision-making; availability of one FDA-approved test.

Other Considerations: EGAPP methods challenged by limited literature and assessment of the grey literature; potential impact on women with breast cancer.