RESUMEN
Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required. Clin Cancer Res; 23(10); 2575-83. ©2016 AACR.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama/genética , Factor 4E Eucariótico de Iniciación/genética , Factores de Iniciación de Péptidos/genética , Proteínas de Unión al ARN/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/diagnóstico , Neoplasias de la Mama Masculina/tratamiento farmacológico , Neoplasias de la Mama Masculina/patología , Supervivencia sin Enfermedad , Everolimus/administración & dosificación , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Imidazoles/administración & dosificación , Masculino , Persona de Mediana Edad , Pronóstico , Quinolinas/administración & dosificación , Caracteres Sexuales , Transcriptoma/genética , Factor 5A Eucariótico de Iniciación de TraducciónRESUMEN
Over the past 35 years, I have witnessed an apparent quest to make nursing into something which it isn't, and to ignore the simple natural healing process which it is. I believe that nursing (nurturing) effectively promotes self-healing.