CYP2D6 genotyping and tamoxifen in the treatment of post-menopausal breast cancer - A reply

摘要

We appreciate the opportunity to clarify further the issues raised by Damkier [1] related to our recent correspondence [2] in which we summarized the available evidence of the prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal women with early breast cancer for the purpose of rectifying current controversies. Damkier takes the position that we failed to discuss original findings by others. However we respectfully disagree that the quoted articles [3, 4] can have an impact on our conclusions. There is no doubt that concordance of genotyping data of germline- and tumour-derived DNA can be achieved in specifically designed studies. However, both quoted studies [3, 4] are irrelevant to the fact in question. In particular, Rae et?al. [3] fall short of demonstrating such concordance in the very same study population of their previously published pharmacogenetic analyses of BIG1-98 [5] or ATAC [6]. With this regard, it is fair to point the uninitiated reader's attention to the complexity of the CYP2D6 polymorphism for which deviation from Hardy–Weinberg equilibrium (HWE) is possible, particularly when formalin-fixed paraffin-embedded (FFPE) tumour tissue is used for genotyping [2, 7]. The criticism raised by us and others is not a deviation from HWE per se but a massive violation in the order of magnitude of 10?92 that can only be explained by severe methodological flaws. Thus, Rae et?al. [3] clearly failed to dispel the doubts on the validity of their previous studies [5, 6].