RESUMO
PURPOSE: Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer. PATIENTS AND METHODS: This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis. RESULTS: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR. CONCLUSION: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer. TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005). ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study were presented in part at the 2016 ESMO conference October 7-11, 2016, Copenhagen, Denmark (oral presentation).
Assuntos
Biomarcadores Tumorais/imunologia , Neoplasias da Mama/imunologia , Contagem de Linfócitos , Neutrófilos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
The effect of injection-drug use on human immunodeficiency virus type 1 (HIV-1) env genetic evolution was examined in 15 seroconverting injection-drug users followed up for 4 years. After adjustment for non-drug-related independent variables significantly associated with genetic diversity (time since seroconversion and progressor status), injection frequency was positively and highly significantly associated with HIV-1 env genetic diversity (P=.003). The mutation rate in those who had injected at least once a day during the previous 6 months was estimated to be 62% greater than the rate in those who had not injected at all. If the positive effect of drug-injection frequency on env genetic diversity extends to the HIV-1 pol gene, the risk of emergence of resistance to antiretroviral drugs may be enhanced by increased drug-injection frequency, especially under the selection pressure of antiretroviral therapy.
Assuntos
Evolução Molecular , Genes env , Soropositividade para HIV/virologia , HIV-1/genética , Abuso de Substâncias por Via Intravenosa/virologia , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Feminino , Anticorpos Anti-HIV/sangue , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/imunologia , HIV-1/isolamento & purificação , Humanos , Masculino , Fatores de TempoRESUMO
The availability of molecular and morphological markers in a parthenogenetically reproducing strain of Drosophila mercatorum allowed us to design an experiment in which we could obtain a sample of completely homozygous recombinant females from two different parental homozygous strains. The phenotypic values of body-size-related measures and bristle numbers (sternopleural and abdominal) were measured in females sampled from the parental, F1 and F2 generations. The DNA extracted from the F2 flies was scored for five Mendelian segregating loci through double stringency PCR. In addition, the flies were scored for three morphological recessive loci. We estimated all single-locus and all two-loci associations between the marker loci with the principal components of the morphological data, which allowed us also to estimate the epistatic parameters. The results suggest that the underlying genetic architecture of the morphological phenotypes cannot be regarded as a result of additivity only, but instead, involves many different kinds of interactions that are distributed around an additive mean.