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TDX (Tesis Doctorals en Xarxa)
Doctoral thesis . 2016
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Recolector de Ciencia Abierta, RECOLECTA
Doctoral thesis . 2016
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Patrones de respuesta a quimioterapia neoadyuvante en cáncer de mama y conservación mamaria

Authors: Pla Farnós, Maria Jesús;

Patrones de respuesta a quimioterapia neoadyuvante en cáncer de mama y conservación mamaria

Abstract

Introducción: La quimioterapia neoadyuvante (QMTN), estándar en el cáncer de mama localmente avanzado, ha extendido su uso al cáncer de mama en estadio inicial. Existen diversos patrones histológicos de respuesta a QMTN: respuesta concéntrica (foco central tumoral, envuelto por fibrosis), repuesta parcheada o en nidos celulares (fibrosis alternando con nidos celulares dispersos) y respuesta Mixta. Objetivos: Determinar que variables clínicas e histológicas determinan el patrón de respuesta a QMTN que favorece y permite la conservación mamaria. Análisis de los patrones de respuesta. Parámetros de predicción del tipo de respuesta, porcentaje de cirugía conservadora, cambios en la técnica quirúrgica y comparación de los volúmenes tumorales y quirúrgicos. Curvas de supervivencia Metodología: 177 cánceres de mama que corresponden a 173 pacientes (4 de casos de cáncer bilateral), tratados con QMTN y cirugía posterior entre 1 febrero de 2010 y Octubre de 2013. Estudio retrospectivo de variables clínicas, revisión de los patrones de respuesta y seguimiento oncológico. Resultados: La tasa de conservación mamaria fue del 67.3 %. La respuesta patológica completa (pCR) fue del 25.5%. Los factores predictores de respuesta completa patológica completa, son: ausencia de multicentricidad, receptor de estrógeno (RE) negativo, el receptor de progesterona (RP) negativo, el Grado histológico 3, Ki 67 > 20 % y sobrexpresión de Her 2. En el estudio multivariado, RE negativo y Her 2. El tipo molecular subrogado que predice respuesta completa es Her 2 positivo. Cuando no existe pCR, el patrón de respuesta más frecuente es en nidos celulares o parcheada (42%), concéntrica (21.9%) y mixta el 8.9%. Los factores predictores de la respuesta concéntrica son, tamaño tumoral de 20% y necrosis tumoral. El tipo molecular subrogado que predice respuesta concéntrica es el triple negativo. En la respuesta concéntrica el porcentaje de cirugía conservadora es superior (78.4% versus 58.1%), es más frecuente la necesidad de marcaje prequirúrgico, la ampliación de márgenes intraoperatoria y el número de márgenes ampliados. A pesar del claro efecto del “downstaging” de la quimioterapia neoadyuvante, no existe una correlación entre el tamaño tumoral oncológico teórico postquimioterapia y el volumen oncológico quirúrgico, siendo el volumen oncológico quirúrgico superior al teórico. Esta correlación es independiente del patrón de respuesta. Con un seguimiento de 33 meses de mediana, solo en el grupo de las respuesta completas existen diferencias en supervivencia global. Conclusiones: Existen variables clínicas que predicen el patrón de respuesta a QMTN. Existe un claro efecto de “downstaging” de los volúmenes tumorales que condicionan cambios en la técnica quirúrgica, pero no modifican los volúmenes quirúrgicos que son independientes del tipo de respuesta. El único patrón que impacta en la supervivencia global es la respuesta complete.

Introduction: Neoadjuvant chemotherapy (NAC), standard treatment for locally advanced breast cancer, is nowadays very common in early breast cancer. Exists different histological response patterns to NAC: concentric response (central tumoral focus, surrounded by fibrosis), patched pattern response or in cell nests (fibrosis and scattered cell nests), mixed response. Objectives: To study which clinical and histological variables determine the response pattern to NAC that allows breast conservation. To analyse: the response patterns, response predictive parameters, percentage of conservative surgery, changes of surgical techniques and comparison between theoretical oncologic post chemotherapy volumes and surgical ones. Analysis of survival curves. Methods: 177 breast cancers that correspond to 173 patients (4 cases with bilateral breast cancer), treated with NAC and posterior surgery between February 1st 2010 and October 2013. Retrospective study of clinical variables, review of response patterns and oncologic follow up Results: Breast conservation rate was 67.3%. Pathologic complete response rate (pCR) was 25.5%. pCR predictive factors were: absence of multicentric tumors, negative estrogen receptor (ER), negative progesterone receptor (PR), histological grade 3, Ki67 >20% and overexpression of Her 2. In the multivariate study, negative ER and Her 2 were predictive factors of pCR. The subrogated molecular type that predicts a complete response was Her 2 overexpression. The most common pattern when there is not pCR, is cell nests or patched (42%), concentric (21%) and mixed (8.9%). The concentric response predictive factors are tumor size 20% and tumor necrosis. The subrogated molecular type that predicts concentric response is the triple negative. In the concentric response there is a superior percentage of conservative surgery (78.8% versus 58.1%), it is more frequent the need of pre surgical marking, surgical margins extension and the number of extended margins. Despite the downstaging effect of neoadjuvant chemotherapy, there is no relation between post-surgery theoretical oncologic tumor size and surgical oncologic volume, being the surgical oncologic volume superior to theoretical one. This correlation is independent from the response pattern. With a mean of 33 months of follow up, only in the complete response group there was a differences in overall survival. Conclusions: It exists clinical variables that predict the response pattern to NAC. It exists a clear downstaging effect of tumor volumes that determines surgical technique changes, but does not modify surgical volumes, that are independents from the response type. The only pattern that has an impact on overall survival is the complete response.

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Spain
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Keywords

618, Resposta patològica completa, Breast cancer, Cáncer de mama, Respuesta patológica completa, Pathologic complete response, Quimioteràpia neoadjuvant, Neoadjuvant chemotherapy, Ciències de la Salut, Càncer de mama, Quimioterapia neoadyuvante

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
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Cancer Research