Patients' Understanding of How Genotype Variation Affects Benefits of Tamoxifen Therapy for Breast Cancer

Abstract

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.

A Scoping Review of Attitudes and Experiences with Pharmacogenomic Testing among Patients and the General Public: Implications for Patient Counseling

“…Of these, 35 met eligibility criteria and were included in the analysis. An additional two articles were identified upon reference review of eligible articles and also included in the analysis, for a final total of 37 articles [ 1 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Figure 1 summarizes the identification and selection process for inclusion.…”

Preliminary Pharmacogenomic-Based Predictive Models of Tamoxifen Response in Hormone-dependent Chilean Breast Cancer Patients

“…Although it is well known that genetic variants in CYP2D6 could explain between 10–20% of these cases and its use as a biomarker for TAM is recommended by the FDA, there is still no agreement on its clinical utility for predicting results in BC, the studies reveal contradictory results and the role of other pharmacokinetic and pharmacodynamic proteins have been poorly studied ( Brauch and Schwab, 2014 ; Brewer et al, 2014 ; Province et al, 2014 ; Binkhorst et al, 2015 ; Goetz et al, 2018 ). Therefore, the present research focused on studying the association between 7 genetic variants in several genes encoding proteins involved in the pharmacokinetics and pharmacodynamics of TAM and response (relapse) and ADRs in TAM-treated hormone-dependent BC women and contributing to the field, generating predictive models that approximate the response of patients according to their genetic-metabolic characteristics.…”

“…Although in the last decade several studies have investigated genetic variants in TAM-metabolizing enzymes that might determine the differences in the response to treatment in patients with BC, there are still controversies about their relationship with the response ( Brauch and Schwab, 2014 ; Brewer et al, 2014 ; Province et al, 2014 ; Binkhorst et al, 2015 ). To address this question, we aimed to study the association among response (relapse and ADR) and 7 genetic variants in genes encoding proteins involved in the pharmacokinetics and pharmacodynamics of TAM ( CYP2D6∗4, CYP3A4∗1B (CYP3A4∗1.001), CYP3A5∗3, SULT1A1∗2, UGT2B7∗2, UGT2B15∗2 and ESRA V364E) in women with hormone-dependent BC and under adjuvant treatment with TAM.…”

Knowledge and understanding of pharmacogenomic testing among patients and health care professionals: A scoping review

“…A study has shown that, during a counseling meeting with simulated clients, greater use of technical terms was associated with lower satisfaction with the discussion [37]. Regarding understanding of hypothetical genotype information, a study [38] reports that female patients believed their genotype would not affect their recurrence risk if they did not take Tamoxifen. If that treatment were prescribed, however, they were more likely to believe their extensive Tamoxifen metabolizer genotype would postively affect their prognosis.…”