Publication: Informe farmacogenético en tratamiento de cáncer de mama con tamoxifeno: aspectos médico-legales
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2019-01-28
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Universidad Complutense de Madrid
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Abstract
La Farmacogenética, definida como la disciplina que estudia las variaciones en la secuencia de ADN en relación con la respuesta a los fármacos, se ha convertido en un área de gran importancia en la medicina personalizada (1) a la hora de prescribir un medicamento con mayor seguridad y eficacia. En este sentido, el tamoxifeno es un modelo que estudiar por su elevada variabilidad interindividual en la respuesta al tratamiento y por ser un fármaco de elección en la hormonoterapia del cáncer de mama receptores estrogénicos positivos (RE+).Según la Sociedad Española de Oncología Médica (SEOM) a, el cáncer de mama es el cáncer más común en mujeres con una incidencia de 26.370 casos nuevos por año, una prevalencia a cinco años de 104.405 casos y una mortalidad de 6.477 mujeres, de los cuales un 76% de los carcinomas primarios son RE+ y sólo responden a la hormonoterapia con tamoxifeno entre un 55-60% (2). Esta variabilidad en la respuesta al tratamiento a la misma dosis puede ser debida en parte a diferencias genéticas interindividuales. El tamoxifeno es un profármaco modulador selectivo que requiere ser metabolizado a sus metabolitos primarios N-desmetil-tamoxifeno y 4-hidroxitamoxifenopor varias enzimas CYP450 (3). Además, estos dos metabolitos son metabolizados a endoxifeno por la enzima CYP2D6 en un 100% y 56%, respectivamente (3). El endoxifeno es considerado como el metabolito activo responsable de los efectos antiestrogénicos del tamoxifeno. Por lo tanto, una asociación entre el genotipo y fenotipo metabólico del gen polimórfico CYP2D6 postula que los análisis farmacogenéticos optimizarán el tratamiento...
Pharmacogenetics, defined as the discipline that studies the variations in the DNA sequence in relation to the response to drugs, has become an area of great importance in the personalized medicine (1) when prescribing a drug with greater safety and efficacy. In this sense, tamoxifen is a model that should be studied because of its high interindividual variability in the response to treatment and because it is a drug of choice in hormone therapy of breast cancer positive oestrogen receptors (ER+). According to the Spanish Society of Medical Oncology (SEOM)a, breast cancer is the most common cancer in women with an incidence of 26,370 new cases per year, a five-year prevalence of 104,405 cases and a mortality of 6,477 women, of whom 76% of primary carcinomas are ER+ and only respond to hormone therapy with tamoxifen between 55-60% (2). This variability in response to treatment at the same dose may be due in part to interindividual genetic differences.Tamoxifen is a selective modulator prodrug that needs to be metabolized to its primary metabolites N-demethyl-tamoxifen and 4-hydroxy-tamoxifen by severalCYP450 enzymes (3). In addition, these two metabolites are metabolized to endoxifenby the enzyme CYP2D6 in 100% and 56%, respectively (3). Endoxifene is the active metabolite responsible for the antiestrogenic effects of tamoxifen. Therefore, an association between the genotype and metabolic phenotype of the CYP2D6 polymorphic gene postulates that pharmacogenetic analyzes will optimize treatment...
Pharmacogenetics, defined as the discipline that studies the variations in the DNA sequence in relation to the response to drugs, has become an area of great importance in the personalized medicine (1) when prescribing a drug with greater safety and efficacy. In this sense, tamoxifen is a model that should be studied because of its high interindividual variability in the response to treatment and because it is a drug of choice in hormone therapy of breast cancer positive oestrogen receptors (ER+). According to the Spanish Society of Medical Oncology (SEOM)a, breast cancer is the most common cancer in women with an incidence of 26,370 new cases per year, a five-year prevalence of 104,405 cases and a mortality of 6,477 women, of whom 76% of primary carcinomas are ER+ and only respond to hormone therapy with tamoxifen between 55-60% (2). This variability in response to treatment at the same dose may be due in part to interindividual genetic differences.Tamoxifen is a selective modulator prodrug that needs to be metabolized to its primary metabolites N-demethyl-tamoxifen and 4-hydroxy-tamoxifen by severalCYP450 enzymes (3). In addition, these two metabolites are metabolized to endoxifenby the enzyme CYP2D6 in 100% and 56%, respectively (3). Endoxifene is the active metabolite responsible for the antiestrogenic effects of tamoxifen. Therefore, an association between the genotype and metabolic phenotype of the CYP2D6 polymorphic gene postulates that pharmacogenetic analyzes will optimize treatment...
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Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 05-10-2018