Key Questions:

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

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

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

• Question 3a: How well does this testing predict recurrence rates for breast cancer compared tostandard 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 diagnosedwith 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.