“The potential benefit of CYP2D6 testing is obvious but has been difficult to establish,” said Dr. Goetz in a news release from Mayo Clinic. “One major reason appears to be the lack of analytical validity. We found that if you use tumor tissue to determine the CYP2D6 genotype a patient was born with, you are going to get it wrong a substantial portion of the time.” Dr. Goetz and colleagues showed that up to 45% of breast cancer tumors lose one of the two parental CYP2D6 alleles the patient had at birth, resulting in a loss of heterozygosity.
For this reason, the two large clinical trials that found no link between CYP2D6 genotype and tamoxifen efficacy may have been distorted. The studies used tumor tissue rather than healthy tissue when genotyping, which does not correctly represent that patient’s true CYP2D6 genotype at birth.