{"id":114753,"date":"2013-11-10T00:00:00","date_gmt":"2013-11-10T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/evaluacion-de-los-cambios-en-la-respuesta-linfocitaria-en-el-microambiente-tumoral-como-factor-pronostico-y-predictivo-de-respuesta-a-la-quimioterapia-neoadyuvante-del-cancer-de-mama\/"},"modified":"2013-11-10T00:00:00","modified_gmt":"2013-11-10T00:00:00","slug":"evaluacion-de-los-cambios-en-la-respuesta-linfocitaria-en-el-microambiente-tumoral-como-factor-pronostico-y-predictivo-de-respuesta-a-la-quimioterapia-neoadyuvante-del-cancer-de-mama","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/oncologia\/evaluacion-de-los-cambios-en-la-respuesta-linfocitaria-en-el-microambiente-tumoral-como-factor-pronostico-y-predictivo-de-respuesta-a-la-quimioterapia-neoadyuvante-del-cancer-de-mama\/","title":{"rendered":"Evaluaci\u00f3n de los cambios en la respuesta linfocitaria en el microambiente tumoral como factor pron\u00f3stico y predictivo de respuesta a la quimioterapia neoadyuvante del c\u00e1ncer de mama"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Mar\u00eda  Elena Garcia Martinez <\/strong><\/h2>\n<p>Introducci\u00f3n y objetivos: la clasificaci\u00f3n molecular del c\u00e1ncer de mama ha puesto de manifiesto las bases moleculares de la heterogeneidad biol\u00f3gica, cl\u00ednica y anatomopatol\u00f3gica del mismo. Existen diversos estudios donde se estudia la posibilidad de una clasificaci\u00f3n inmunohistoqu\u00edmica &quot;equivalente&quot; a la clasificaci\u00f3n molecular, aunque, otros trabajos han cuestionado la existencia de una correlaci\u00f3n adecuada entre ambas. El microambiente tumoral y m\u00e1s concretamente la infiltraci\u00f3n linfocitaria peritumoral (til) han sido relacionados con la respuesta al tratamiento de quimioterapia. Los desequilibrios entre las distintas poblaciones de c\u00e9lulas inmunes, como los linfocitos t reguladores, pueden justificar algunos de los mecanismos en la progresi\u00f3n tumoral. Los objetivos de este estudio son: 1). Evaluaci\u00f3n del tipo de infiltraci\u00f3n tumoral linfocitaria previa al tratamiento con qtn en el c\u00e1ncer de mama, definida por las subpoblaciones t (cd3, cd4, cd8 y treg (foxp3)), subpoblaciones b (cd20) y macr\u00f3fagos (cd68). Evaluaci\u00f3n de las modificaciones del infiltrado inmune tras la quimioterapia neoadyuvante. 2). Determinaci\u00f3n del valor predictivo para la respuesta a la qtn y del valor pron\u00f3stico de las modificaciones inducidas por la quimioterapia en la infiltraci\u00f3n linfocitaria tumoral. material y m\u00e9todos: se ha analizado una serie de 121 pacientes diagnosticadas de c\u00e1ncer de mama estadio ii-iii, en tratamiento con qtn con esquema secuencial de antraciclinas y taxanos. La clasificaci\u00f3n ihq utilizada, es la que se utiliza en la pr\u00e1ctica asistencial habitual (re+ y\/0 rp+ y her2- (hormonosensibles); re+ y\/o rp+ y her2+ (hormonosensibles her2+); re &#8211; y rp=- y her2+ (her2+); re- y rp- y her2- (triple negativo). para el an\u00e1lisis de til cd4, cd8, cd3, cd20, foxp3 y cd68 se ha realizado un microarray de muestras apareadas pre y post-qt, as\u00ed como determinaciones inmunohistoqu\u00edmicas de los til. Adem\u00e1s se han escaneado y digitalizado las muestras y posteriormente hemos realizado un an\u00e1lisis morfom\u00e9trico ajustado al \u00e1rea tumoral con el programa image j. Para el an\u00e1lisis estad\u00edstico hemos utilizado el programa spss 15.0 resultados: los an\u00e1lisis por subgrupos ihq de c\u00e1ncer de mama realizados, tanto descriptivos como en relaci\u00f3n con la tasa de rcp, son congruentes con lo publicado en la literatura.  son  factores predictivos de rcp independientes, tanto la infiltraci\u00f3n linfocitaria tumoral basal alta por cd3, cd4 y cd20, como,  y m\u00e1s significativos que la propia infiltraci\u00f3n, los descensos que se producen en estas poblaciones linfocitarias con la qtn. Ratios elevados de cd4\/cd8 y foxp3\/cd8 pre-qt son tambi\u00e9n factores predictivos de rcp. La ausencia de cd20 pre-qt es factor predictivo de quimiorresistencia. Son factores pron\u00f3sticos para sg, sle y sled, no s\u00f3lo la infiltraci\u00f3n basal alta por cd3, sino tambi\u00e9n, y con mayor relevancia, el descenso de cd3 producido por la qt. por otro lado,  las infiltraciones altas por cd68 en el tumor residual se podr\u00edan asociar a peor pron\u00f3stico en pacientes diagnosticadas de c\u00e1ncer de mama. conclusiones: en el c\u00e1ncer de mama estadio ii-iii en tratamiento con qtn, al margen de los factores predictivos y pron\u00f3sticos cl\u00e1sicos dependientes del propio tumor, existen otros factores predictivos de respuesta y pron\u00f3sticos, independientes de las anteriores, en \u00edntima relaci\u00f3n con la infiltraci\u00f3n por c\u00e9lulas inmunes existente en el microambiente tumoral. el conocimiento del perfil de respuesta inmune tumoral en cada paciente permitir\u00eda una mejo selecci\u00f3n de las pacientes para el manejo neoadyuvante, as\u00ed como la detecci\u00f3n de subgrupos de pacientes con peor pron\u00f3stico en las que, adem\u00e1s del tratamiento convencional, podr\u00edan plantearse nuevas estrategias terap\u00e9uticas dirigidas a dianas relacionadas con la modulaci\u00f3n de la respuesta inmune antitumoral.    background and objetives: the molecular classification of breast cancer has highlighted the molecular bases of biological, clinical and pathological breast cancer heterogeneity. The possibility of a immunohistochemical classification equivalent to molecular classification has been developed by several authors, nevertheless, an adequate correlation between both classifications has been questioned. The association of tumor microenvironment, specifically tumor infiltrating lymphocytes (til), with the outcome after breast cancer neoadjuvant chemotherapy has been suggested by several studies. The unbalance between til subpopulation, as t-reg lymphocytes, could explain some of the mechanisms of tumoral progression. The objectives of this study are: 1). Evaluation of the type of tumor infiltrating lymphocytes before neoadjuvant chemotherapy in breast cancer, defined by t subpopulation (cd3, cd4, cd8 and treg (foxp3)), b subpopulation (cd20) y macrophage (cd68) 2). Evaluation of the predictive value for response to chemotherapy and the prognostic value of til variations induced by the neoadjuvant chemotherapy. material and methods: til and cd68 cells have been analyzed in pre- and post-chemotherapy biopsies of 121 breast cancer ii-iii patients treated with neoadjuvant chemotherapy (80.4% sequential ac-docetaxel). The immunohistochemical classification used is the same we use in our clinical practice (re+ and\/or rp+ and her2- (hormone-sensitive); re+ and\/or rp+ and her2+ (hormone-sensitive her2+); re &#8211; and rp- and her2+ (her2+); re- and rp- and her2- (triple negative). A tissue microarray with paired pre- and post-treatment biopsies was built, and stained with immunohistochemistry (ihc) for cd3, cd4, cd8, cd20, foxp3 and cd68. Morphometric analysis (til count\/mm2) was performed after slide scanning and digitalization. Statistical analysis was done with spss 15.0 software. results: the results of the analysis by immunohistochemical breast cancer subgroups, both descriptive and related with pathological complete response, are similar with the results communicated in the literature. Higher pre-treatment cd3, cd4 and cd20 til, as well as high ratio cd4\/cd8 and foxp3\/cd8, predict pathologic complete response in patients with invasive breast cancer receiving anthracyclines and taxanos neoadjuvant chemotherapy. Aditionally the decrease of til with chemotherapy is an independent predictive factor of pathologic complete response. Absence of cd20 pre-treatment predicts chemorresistance. Higher cd3 pre-treatment and cd3 variations induced by chemotherapy are related with prognosis in patients with invasive breast cancer.Higher infiltration of residual tumor by cd68 could be associated to worse prognostic in breast cancer patients. conclusions: besides traditionally predictive and prognosis factors in breast cancer ii-iii with neoadjuvant treatment, there are other predictive and prognosis factors related to immune tumor microenvironment. These results suggest that the degree of immune modulation by neoadjuvant treatment has an impact on survival and, might be useful for prognostic classification in the setting of breast cancer treated with neoadjuvant treatment. We could use it to select poor prognosis patients to offer new immune modulation treatment besides neoadjuvant chemotherapy.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Evaluaci\u00f3n de los cambios en la respuesta linfocitaria en el microambiente tumoral como factor pron\u00f3stico y predictivo de respuesta a la quimioterapia neoadyuvante del c\u00e1ncer de mama<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Evaluaci\u00f3n de los cambios en la respuesta linfocitaria en el microambiente tumoral como factor pron\u00f3stico y predictivo de respuesta a la quimioterapia neoadyuvante del c\u00e1ncer de mama <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Mar\u00eda  Elena Garcia Martinez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 11\/10\/2013<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Francisco De Asis Ayala De La Pe\u00f1a<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: ana Lluch hernandez <\/li>\n<li>montserrat Mu\u00f1oz mateu (vocal)<\/li>\n<li>Jos\u00e9 Aguilar jimenez (vocal)<\/li>\n<li>\u00e1lvaro Rodriguez lescure (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Mar\u00eda Elena Garcia Martinez Introducci\u00f3n y objetivos: la clasificaci\u00f3n molecular del c\u00e1ncer de mama ha puesto de [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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