The study by Okishiro et al 1 concludes that the cytochrome P450 (CYP) genotype CYP2D6*10/*10 is unlikely to have a clinically significant impact on prognosis in women with breast cancer who receive adjuvant tamoxifen.
However, several aspects of the study by Okishiro et al call their conclusions into question and raise serious doubts whether a statistical review was performed as part of the peer-review process.
First, questions exist regarding the makeup of the authors' cohort, including the number of patients who either refused consent or did not undergo blood collection. Furthermore, because the timing of blood collection is not specified, there would be great opportunity for bias if patients were identified and blood collection was initiated months or years after surgery, in that the patients who developed recurrent disease and/or died would not have been included. The authors did not provide the rationale for including patients who had estrogen receptor-negative disease (for which tamoxifen is not effective) or patients who also received chemotherapy (which reduces the likelihood of a breast event and, thus, the statistical power). The consistency of the surveillance schedule and the documentation needed to verify disease progression were not addressed. Finally, the number of patients who could not be located, the number of disease progressions, and the number deaths without progression were not provided.
Despite these issues, the most disconcerting aspect of this report is that the authors were not required to provide the smallest detectable hazard ratio given their study characteristics. Compared with CYP2D6 extensive metabolizers, poor metabolizers exhibit a 3fold higher risk of recurrence, 2,3 whereas CYP2D6 intermediate metabolizers (those with ''intermediate'' reductions in endoxifen concentrations) exhibit a lower risk of recurrence. [2][3][4][5] Given the characteristics of the study by Okishiro et al (median follow-up, 56 months among 173 patients, with 25% with the *10/*10 genotype; enrollment period, 6 years; follow-up, 4 years; and 5-year recurrence-free survival rate, 90% in the *10/*10 genotype subgroup), a 2-sided a ΒΌ .05 logrank test has a power of 26% to detect a 2-fold increase in the hazard of disease recurrence in the *10/*10 carriers relative to *10/wild type (wt) or wt/wt carriers.
The relation between the CYP2D6*10 genotype and recurrence in tamoxifen-treated patients is an important question that the study by Okishiro et al is neither designed nor statistically powered to answer.