Table 3.

Pharmacogenomic applications: Summary of current evidence for breast cancer case studies

			Comparative Effectiveness Research (CER)
Test Application	Analytic Validity QUESTION: How well can we measure [test application]?	Clinical Validity QUESTION: Is [test application] associated with the treatment response?	Clinical Utility QUESTION: What are the benefits and harms of [test application] for treatment decisions?	Added Clinical Value QUESTION: Is use of [test application] better than the alternative?
HER2 genotype and trastuzumab treatment response	• RESULT: Test characteristics depend on whether IHC or FISH platform is used, test volume of the laboratory, and testing strategy (e.g., FISH or IHC test first) • APPROACH: observational stu dies • LIMITATIONS: HER2 status may change when comparing the prima rytumor to metastases.	• RESULT: HER2 status is associated with survival following treatment with trastuzumab in early stage and metastatic disease, and with response to anthracyclines. • APPROACH: randomized clinical trials • LIMITATIONS: some studies on anthracyclines had small samples sizes	• HARMS: potential for trastuzumab to be effective for some (small %) patients who are HER2 negative • BENEFITS: Avoiding cardiotoxic side effects in patients who will not respond to trastuzumab. • Avoiding use of an expensive treatment for patients who will not benefit from treatment	• COMPARATOR: herceptin treatment decisions in the absence of knowledge of HER2 status • RESULT: none. • APPROACH: none. • LIMITATIONS: none.
CYP2D6 genotype and tamoxifen treatment response	• RESULT: High for SNP detection • APPROACH: observational studies • LIMITATIONS: none.	• RESULT: Not well established; conflicting results • APPROACH: retrospective analysis of prospective clinical trials and retrospective cohort studies • LIMITATIONS: small to medium sized studies; conflicting	• HARMS: unknown. • BENEFITS: Alternative treatments for women with poor metabolizer ge notypes(aromatase inhibitors) • Tamoxifen could become the preferred effective and inexpensive therapy for many women without poor metabolizer genotypes	• COMPARATOR: treatment decisions in the absence of knowledge of CYP2D6 genotype • RESULT: none. • APPROACH: none. • LIMITATIONS: Direct assessment of clinical utility with RCT expensive