RESUMO
Tamoxifen is a mainstay in the treatment of hormone-receptor sensitive breast cancer. To be effective, it needs conversion into 4-hydroxy-tamoxifen and endoxifen. The key enzyme involved is encoded by the gene CYP2D6 of which several, sometimes population-specific alleles are known. Corresponding enzyme variants may result in poor, intermediate, and extensive metabolization and therefore different steady-state plasma levels of active metabolites. Those are hypothesized to be linked to clinical outcomes of tamoxifen therapy. However, a wealth of mostly retrospective cohort studies came up with conflicting results. Appraisal of these studies is difficult and a metaanalysis impossible due to heterogeneity of patient populations, disease factors, treatment modalities, and measured outcomes. As standardization would not overcome intrinsic limitations of retrospective analyses, prospective trials comparing genotype-guided versus unsighted tamoxifen treatment are required to prove whether routine CYP2D6 genotyping is clinically effective and cost-effective.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Citocromo P-450 CYP2D6/genética , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/genética , Polimorfismo Genético/genética , Tamoxifeno/uso terapêutico , Alelos , Antineoplásicos Hormonais/farmacocinética , Neoplasias da Mama/etnologia , Estudos de Coortes , Etnicidade/genética , Feminino , Deleção de Genes , Frequência do Gene/genética , Testes Genéticos , Genótipo , Humanos , Tamoxifeno/farmacocinética , Resultado do TratamentoRESUMO
BACKGROUND: The VCS technology of Beckman Coulter differentiates white blood cells based on measures of their volume, conductivity and light scatter. The current study investigated the predictive value of index measures, known as research population data, for the detection of chronic lymphatic leukemia and myelodysplastic syndrome. METHODS: Blood cell counts were performed in samples from 44 patients with chronic lymphatic leukemia, 19 patients with myelodysplastic syndrome and 199 healthy blood donors using the Beckman Coulter LH750. Means and standard deviations of volume, conductivity and scatter of lymphocytes and neutrophils were evaluated as predictors for both diseases. Their specificity and selectivity were evaluated by logistic regression and receiver operating characteristic curve analysis. RESULTS: Research population data were significantly different among groups. For chronic lymphatic leukemia, standard deviations of lymphocytes scatter and volume showed most relevant differences in comparison to healthy blood donors (sensitivity 88.6%, specificity 84.4%). For myelodysplastic syndrome, standard deviations of neutrophils conductivity were most predictive (sensitivity 73.7%, specificity 93.0%). Areas under corresponding receiver operating characteristic curves were 0.941 and 0.951, respectively. CONCLUSIONS: Based on their high predictive value, research population data could be routinely used to screen for chronic lymphatic leukemia and myelodysplastic syndrome.