BACKGROUND: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. METHODS: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). RESULTS: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). CONCLUSION: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.
BACKGROUND:CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. METHODS:Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). RESULTS:Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). CONCLUSION:Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.
Authors: William J Irvin; Christine M Walko; Karen E Weck; Joseph G Ibrahim; Wing K Chiu; E Claire Dees; Susan G Moore; Oludamilola A Olajide; Mark L Graham; Sean T Canale; Rachel E Raab; Steven W Corso; Jeffrey M Peppercorn; Steven M Anderson; Kenneth J Friedman; Evan T Ogburn; Zeruesenay Desta; David A Flockhart; Howard L McLeod; James P Evans; Lisa A Carey Journal: J Clin Oncol Date: 2011-07-18 Impact factor: 44.544
Authors: C Lerman; C Hughes; R T Croyle; D Main; C Durham; C Snyder; A Bonney; J F Lynch; S A Narod; H T Lynch Journal: Prev Med Date: 2000-07 Impact factor: 4.018
Authors: Neal J Meropol; Kevin P Weinfurt; Caroline B Burnett; Andrew Balshem; Al B Benson; Liana Castel; Sandra Corbett; Michael Diefenbach; Darrell Gaskin; Yun Li; Sharon Manne; John Marshall; Julia H Rowland; Elyse Slater; Daniel P Sulmasy; David Van Echo; Shakira Washington; Kevin A Schulman Journal: J Clin Oncol Date: 2003-07-01 Impact factor: 44.544
Authors: Carla Miranda; Macarena Galleguillos; Roberto Torres; Karla Tardón; Dante D Cáceres; Kuen Lee; María A Redal; Nelson M Varela; Luis A Quiñones Journal: Front Pharmacol Date: 2021-11-25 Impact factor: 5.810