It seems that we are living in an era of gene-driven medicine, hoping it will not drive us crazy or make us simply less efficient. Though the contribution of Lim et al, 3 gives us a better understanding on why some women do not respond to a widely used therapeutic, the clinical implications are not yet well defined. These points do not limit the scientific value of that article, particularly the interesting and brilliant hypothesis to be tested about the “demonstrated superior efficacy” of aromatase inhibitor compared with tamoxifen. 5 Few tests might impact public health, 6 and currently the main reason for rejection is insufficient evidence for clinical utility. The issue of the validation of genetic testing before diffusion is critical. If none of these criteria is fulfilled, the value added by the genetic testing should be low (if any), and the need for a change in clinical practice, doubtful. Lastly, a genetic test that will predict a wide range of effects (such as the biotransformation of many drugs) could also be used. 4 It could also be a better collective choice if cheaper, simpler, or faster. Shifting to gene testing is an absolute necessity to preclude irreversible events like dreadful adverse effects of drugs. The dosage of the critical product (the active metabolite) should in that case be more accurate, concerning both calibration and discrimination. It is unlikely to expect an improved discrimination, because plasma concentration of active metabolite is the end-product of many steps, each of them partially under genetic determinism: absorption, biotransformation from inactive to active product, and elimination of the active product (partially discussed in the article). Figure 3 tells us that CYP2D6 does predict outcome, but does it do it better than plasma concentration at steady-state stage? These data are available in that survey, and therefore comparative analysis should be disclosed. The rule of Ockham, “ Pluralitas non est ponenda sine necessitate,” means that new entities are required only if necessary. Does having a surrogate (CYP2D6) for that surrogate, improve care and challenge current clinical practice? A close surrogate, used in this contribution, is the concentration of active metabolites. With regard to the contribution of Lim et al, 3 I will challenge neither the validity nor the scientific value of this article but rather the meaning of the title “Clinical implication.” It is crystal clear that the real end point, the gold standard, is the individual effectiveness of the treatment, tamoxifen in that case. Gene analysis, both somatic and germline, could help to achieve that goal however, having a hammer in the hand does not mean everything is a nail. We live in societies with more and more focus on the individuals, 1 who claim for individualized care and prevention. Not surprisingly, genes-its biologic component-are used for understanding the past and reading the future. Heredity has been both an explicative and a predictive tool for a long time.
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