Practice and Attitudes towards CYP2D6 Testing for Patients on Tamoxifen among US Oncologists.

Abstract

Abstract Background: CYP2D6 genotype has been associated with breast cancer outcomes for patients on Tamoxifen (TAM) and testing is commercially available. In the context of emerging data regarding the clinical relevance of CYP2D6 testing (CYPT) and uncertainty regarding how test results should be used in practice, we evaluated current practice and attitudes with regard to this novel pharmacogenomic test among U.S. oncologists.Methods: A survey was mailed to all breast cancer oncologists identified at National Comprehensive Cancer Network (NCCNO) centers and a random sample of community based oncologists (CBO) identified from the American Society of Clinical Oncology directory. The survey evaluated knowledge of the CYP2D test, use of the test, requests for the test by patients and third parties, and response to hypothetical test results. Associations between practice setting and CYP2D6 knowledge, CYPT, and practice patterns were evaluated. All statistical tests were two-sided.Results: 201 of 459 (44%) oncologists responded, including 97/173 (56%) of NCCNO and 104/286 (36%) of CBO. While 90% of all oncologists were aware of CYPT, only 31% had ever ordered CYPT, and only 14% used CYPT for ≥ 10% of patients on TAM. 22% had received a request for CYPT from a 3rd party. While NCCNO were more likely to be aware of CYPT (98% vs. 82%, p < 0.001), and to receive requests for CYPT (33% vs. 12%, p < 0.001), CBO reported higher frequency of CYPT in routine practice (21% vs. 11%, p = 0.06). Despite rare use, 66% of CBO and 44% of NCCNO reported they would order the test upon patient request (p < 0.001). In hypothetical scenarios involving CYPT for patients on TAM, for premenopausal women with poor metabolism, 33% would make no change, while 38% would switch to ovarian suppression (OS) plus aromatase inhibitor (AI), 9% would switch to OS alone, and 8% would add OS to TAM. CBO were more likely to switch to OS + AI in this setting (47% vs. 31%, p < 0.02), while NCCNO were more likely to recommend no change (50% vs. 18%, p < 0.001). For premenopausal intermediate metabolizers, 33% of CBO would change management, compared to 8% of NCCN (p < 0.001), with addition of OS to TAM being most frequent among both groups. For postmenopausal women with poor metabolism the majority of both CBO and NCCNO would switch to AI (82% vs. 71%, p = 0.08). Among oncologists who indicated they might change management based on CYPT results, 43% had never ordered the test. Respondents cited data from randomized trials, and professional guidelines as most influential for decisions regarding ordering tests.Conclusion: Despite calls for increased CYP2D6 testing at academic meetings and occasional requests by 3rd parties, use of CYPT is currently infrequent in oncology practice. Greater familiarity with breast cancer management correlated with lower use of CYPT and greater reluctance to change management based on test results at this time. Diversity in practice patterns and knowledge suggests a need for greater consensus on CYPT in routine practice, and highlights the need for further clinical research in this area. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1077.