Pharmacogenetic testing in the face of unclear clinical efficacy: Lessons from cytochrome P450 2D6 for tamoxifen

Abstract

This study evaluated self-reported knowledge, practice, and attitudes toward commercially available cytochrome P450 2D6 (CYP2D6) pharmacogenomic testing for patients on tamoxifen for breast cancer (CYPT) among US oncologists while evidence for the use of the test was evolving. A self-administered survey of medical oncology breast cancer specialists at National Comprehensive Cancer Network (NCCNO) centers and a random sample of community-based oncologists (CBOs) was undertaken. The survey evaluated knowledge and use of the CYP2D6 test and response to hypothetical test results. In total, 201 of 459 (44%) oncologists responded. At a time when CYPT remained experimental, 31% of oncologists reported use of CYPT and 56% reported willingness to order CYPT outside of a clinical trial if requested by a patient. Compared to oncologists specializing in breast cancer, oncologists in community-based practice were more likely to use CYPT routinely (21% versus 11%, P< .06), to order CYPT on patient request (66% versus 44%, P< .001), and to change management for premenopausal women with intermediate metabolism (34% CBO versus 8% NCCN, P< .001). Oncologists cited data from randomized trials and professional guidelines as most influential when considering use of a genetic test. Prior to definitive evidence, a minority of oncologists reported using the CYP2D6 test routinely, and many indicated willingness to change management of patients based on test results. There is a need to educate clinicians and the public regarding the uncertain benefits of commercially available genetic tests in clinical practice when evidence from ongoing trials is still emerging.