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Fotocópia
Id: 182276
Autor: Baena Cañada, José M; Gámez Casado, Salvador; Rodríguez Pérez, Lourdes; Quílez Cutillas, Alicia; Cortés Carmona, Cristina; Rosado Varela, Petra; Estalella Mendoza, Sara; Ramírez Daffós, Patricia; Benítez Rodríguez, Encarnación.
Título: Evaluación del riesgo clínico, no genómico y resultados de supervivencia en el carcinoma de mama hormonosensible, HER-2 negativo, con ganglios negativos / Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, lymph node negative breast cancer
Fonte: Med. clín (Ed. impr.);151(12):469-475, dic. 2018. graf, tab.
Idioma: es.
Resumo: Antecedentes y objetivos: En el cáncer de mama hormonosensible, HER-2 negativo, con ganglios negativos, la presencia de un riesgo genómico bajo permite tratar solo con hormonoterapia adyuvante, obteniendo unas excelentes tasas de supervivencia. La justificación de este estudio es demostrar que también se obtienen unas excelentes tasas de supervivencia tratando solo con hormonoterapia adyuvante mediante la evaluación del riesgo clínico. Pacientes y métodos: Estudio descriptivo, observacional y retrospectivo entre 2006 y 2016 de la cohorte de cáncer de mama hormonosensible, HER-2 negativo, con ganglios negativos, tamaño del tumor mayor de 1cm o entre 0,6 y 1cm con características desfavorables. Revisión retrospectiva de los registros de salud. Datos de mortalidad del Registro Nacional de Defunciones. Resultados: Un total de 203 pacientes fueron evaluables para la supervivencia. Ciento veintitrés (60,50%) fueron tratadas solo con hormonoterapia adyuvante, 77 (37,90%) con quimioterapia-hormonoterapia, una (0.50%) solo con quimioterapia y 2 (1%) no recibieron ningún tratamiento. La tasa de supervivencia global a los 5 años fue del 97% (intervalo de confianza [IC] del 95% 94-100). La tasa de intervalo libre de metástasis a distancia fue del 94% (IC 95% 90-98). En el subgrupo de pacientes tratadas solo con hormonoterapia la tasa de supervivencia global y del intervalo libre de metástasis a distancia a los 5 años fue del 98% (IC 95% 95-100) y 97% (IC 95% 93-100), respectivamente. Conclusiones: Las pacientes con cáncer de mama hormonosensible, HER-2-negativo, con ganglios negativos, tratadas solo con hormonoterapia según su riesgo clínico, obtienen resultados de supervivencia similares a los descritos cuando son tratadas solo con hormonoterapia según su riesgo genómico

Background and objectives: In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. Patients and methods: A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. Results: A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Conclusions: Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk
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Id: 173730
Autor: Lin, X; Wang, Y.
Título: Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression
Fonte: Clin. transl. oncol. (Print);20(11):1400-1407, nov. 2018. ilus, graf.
Idioma: en.
Resumo: Purpose: Her-2 is an epidermal growth factor receptor expressed in some prostate cancers (PC) associated with outgrowth of the tumor. Dysregulation of some microRNAs is involved in the regulation of PC pathogenesis, whereas the role of miR-4319 in PC is unknown and addressed in the current study. Methods: The levels of miR-4319 in PC tissues were determined by RT-qPCR and their association with patient survival was studied by Kaplan-Meier analysis. Targeted genes for miR-4319 were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. Growth of cells of overexpression or inhibition of miR-4319 or Her-2 was analyzed by an MTT assay. Cell survival in response to a chemotherapeutic drug, estramustine (EM), was analyzed by CCK-8 assay. Cell apoptosis was evaluated by TUNEL assay and Western blotting for apoptosis-associated proteins. Results: MiR-4319 levels were decreased in PC specimens, compared to corresponding normal prostate tissue. Lower levels of miR-4319 were correlated with poorer overall patients' survival. In vitro, the cell survival mediated with Her-2 against chemotherapy was inhibited by overexpression of miR-4319 and was enhanced by depletion of miR-4319. Depletion of miR-4319 in primary prostate epithelial cells increased Her-2-dependent cell growth, while re-expression of miR-4319 in PC cells inhibited Her-2-dependent cell growth and Her-2-dependent resistance to EM-induced apoptosis. Conclusion: The growth and chemo-resistance of PC cells may be suppressed via re-expression of miR-4319 that inhibits Her-2 signaling

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Id: 170560
Autor: Wang, Y; He, L; Cheng, Y.
Título: An independent survival prognostic role for human epidermal growth factor receptor 2 in gastric cancer: evidence from a meta-analysis
Fonte: Clin. transl. oncol. (Print);20(2):212-220, feb. 2018. tab, ilus.
Idioma: en.
Resumo: Background. Some studies have suggested that human epidermal growth factor receptor 2 (HER2) positive is associated with poor outcomes in gastric cancer (GC), whereas another inconsistent studies make the situation confused. This meta-analysis was performed to determine whether HER2 played an independent prognostic role in clinicopathological characteristics and survival outcomes of GC. Patients and methods. Combination of GC and human epidermal growth factor 2 or HER2 or HER2/neu or erbB-2 or cerbB-2 or c-erbB2 or CD340 or p185 were used as key words. Data were compared according to the HER2 status. Time-to-event outcomes of overall survival (OS) were analyzed using Hazard Ratios (HRs) with fixed effect, while 5-year survival rate and clinicopathological factors were performed using odd ratios (OR) with random effect. Results. Nighteen trials, from 1986 to October 2013, were identified by two independent authors. A total of 6344 GC patients were included in this meta-analysis, with 1148 HER2 protein overexpression or gene amplification. Comparison of 5-year survival of patients with HER2-positive status versus HER2-negative status showed that OR was 0.58 [95% confidence interval (CI), 0.37-0.91], and the result was significant (P = 0.02). The survival outcome of HER2 protein overexpression or gene amplification patients was worse than those with normal HER2 (HR 1.15; 95% CI 1.12-1.18; P < 0.00001). However, the difference of III-IV stage ratio between HER2-positive and HER2-negative patients was not significant (OR 1.44; 95% CI 0.95-2.18; P = 0.09) even in the subgroup analysis of Asia (P = 0.12 and Europe (P = 0.51). Conclusion. HER2 protein overexpression or gene amplification in GC patients is associated with a poor survival outcome, and may play a role in GC tumorigenesis (AU)

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Id: 169439
Autor: Bernet Vegué, Laia.
Título: La genómica en cáncer de mama: nuevas perspectivas / Genomics in breast cancer: new directions
Fonte: Rev. senol. patol. mamar. (Ed. impr.);30(4):141-142, oct.-dic. 2017.
Idioma: es.
Resumo: No disponible
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Id: 168907
Autor: Lopez-Vivanco, G; Salvador, J; Diez, R; López, D; Salas-Cansado, M de; Navarro, B; Haba-Rodríguez, J de la.
Título: Cost minimization analysis of treatment with intravenous or subcutaneous trastuzumab in patients with HER2-positive breast cancer in Spain
Fonte: Clin. transl. oncol. (Print);19(12):1454-1461, dic. 2017. ilus, tab, graf.
Idioma: en.
Resumo: Purpose. To describe healthcare professional (HCP) and patient time and related costs associated with trastuzumab intravenous infusion (IV) and trastuzumab subcutaneous (SC) formulations in patients with HER2-positive early breast cancer. Methods. This prospective, observational time, and motion study in three Spanish centers was run as a substudy of the PrefHer trial. We recorded active HCP time for trastuzumab SC and IV-related tasks and calculated HCP time as the mean sum of task times over 154 administrations (80 IV, 74 SC). We calculated mean patient infusion chair time and treatment room time. Staff costs were calculated using fully loaded salary costs based on Spanish salaries (Euros 2012). Results. The transition from trastuzumab IV to SC led to a 50% reduction in active HCP time [27.2 min (95% CI 21.8-32.6) vs. 13.2 min (95% CI 8.9-17.5) per cycle]. Time savings resulted from avoiding IV catheter installation and removal, line flushing, and drug reconstitution. SC administration led to a fivefold reduction (78-85%) in chair time and a fourfold reduction (59û81%) in patient treatment room time, resulting in 24 h free-up time in the total treatment course (18 cycles). Total estimated direct costs were Euros 29,431.75 and Euros 28,452.12 for IV and SC, respectively, a saving of EUROS 979.60 over a full treatment course. Conclusions. Trastuzumab SC provided substantial time savings for HCP and patients, and reduced staff costs vs. trastuzumab IV. Reducing the use of hospital facilities may result in further savings and improved quality of medical care (AU)

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Id: 158070
Autor: Avendaño López, M del Carmen.
Título: Relevancia biológica de un misterioso grupo hidroxilo / Biological relevance of a mysterious hydroxyl group
Fonte: An Real Acad Farm = An. R. Acad. Farm. (Internet) = An. R. Acad. Farm;82(3):274-282, jul.-sept. 2016. ilus.
Idioma: es.
Resumo: La evolución lleva consigo la pérdida de diversos genes ancestrales, siendo relevante la inactivación en los seres humanos del gen GMAH que nos hace genéticamente incapaces para producir el ácido siálico N-glicolilneuramínico (Neu5Gc). Este ácido se comporta como un antígeno extraño si se incorpora a los tejidos a partir de componentes alimentarios, pudiendo interaccionar con anticuerpos humanos anti-Neu5Gc y promover inflamación y cáncer. Xenotrasplantes, células madre y medicamentos de origen biológico pueden estar contaminados con Neu5Gc. El conocimiento de las interacciones de enlace en el anticuerpo monoclonal 14F17, capaz de discriminar el antígeno tumoral Nglicolil GM3 de su análogo N-acetilado debido a la presencia de un grupo hidroxilo adicional, está dando algunas claves de este fenómeno, cuya aplicación podría ser de interés en la inmunoterapia del cáncer

Evolution is linked to gene loss, being of biological relevance the inactivation of CMAH gene which made humans genetically unable to produce the sialic acid N-glycolylneuraminic (Neu5Gc). This acid acts as a foreign antigen after incorporation into tissues from dietary components, interacting with human antiNeu5Gc antibodies thus promoting inflammation and cancer progression. Xenotransplants, stem cells and drugs of biological origin may be contaminated by Neu5Gc. The binding chemistry of the monoclonal antibody 14F17, which is able to discriminate the tumorspecific antigen N-glycolyl GM3 from the closely related N-acetyl GM3 on the basis of the presence of a single additional hydroxyl group in the former, reveals some clues of this phenomenon that could be of interest in new cancer immunotherapy approaches
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Id: 155901
Autor: Alvarado-Cabrero, Isabel; Kiyokawa, Takako; Piña, Patricia; Valencia-Cedillo, Raquel; Santiago-Payán, Héctor; Stolnicu, Simona.
Título: HER2/neu, p53, MIB1 and PAX8 immunoexpression in Primary Serous Fallopian Tube Carcinomas / Determinación inmunohistoquímica de HER2/neu, p53, MIB1 y PAX8 en el Carcinoma Seroso Primario de la Trompa Uterina
Fonte: Rev. esp. patol;49(4):219-225, oct.-dic. 2016. tab, ilus.
Idioma: en.
Resumo: Background. Carcinoma of the fallopian tube is a rare gynecological malignancy. A previous review of Primary Fallopian Tube Carcinoma (PFTC) from a multi-institutional study identified several poor prognosis indicators, including the depth of invasion, advanced stage disease, tumor grade and the presence of lymph node metastases. The detection of the malignant lesion at an early stage and the identification of biomarkers with prognostic significance are the major concerns of recent studies. Aims. In this study, we have investigated the immunohistochemical expression of 4 proteins in cases of low-grade (n:5) and high-grade (n:65) serous PFTC to determine their role in PFTC prognosis. Material and methods. HER2/neu, p53, PAX8 and MIB-1 were evaluated using immunohistochemistry on a tissue microarray of 70 serous PFTC and the expression was correlated to the following clinico-pathologic variants: age, grade, lymph node metastases, stage and survival. Results. HER2/neu oncoprotein overexpression was demonstrated in 20 of 65 (31%) high-grade serous fallopian tube carcinomas. p53 was demonstrated in more than 50% (3+) of the tumor in 59 (90.7%) high-grade serous FTCs, while eight cases (12%) were moderate or weakly positive (2+). The expression of PAX8 was positive in 55 (78.5%) cases, the remaining 15 (21%) cases being negative. The outcome of the disease for patients with tumors showing HER2/neu overexpression was worse (p:0.0001). p53, MIB-1 or PAX8 failed to have a predictive value in disease outcome. Conclusion. The potential prognostic relevance of HER2/neu in tubal cancer and its potential role in the selection of patients for targeted therapy should be investigated further (AU)

Introducción. El carcinoma de la trompa uterina (TU) es una neoplasia poco frecuente del tracto ginecológico. Una revisión previa de los carcinomas primarios de la TU, en un estudio multiinstitucional, identificó varios factores de mal pronóstico, incluyendo profundidad de invasión, estadio avanzado, grado histológico y presencia de ganglios linfáticos metastásicos. Detectar esta neoplasia en estadios tempranos e identificar biomarcadores con significado pronóstico ha sido el objetivo de los últimos estudios. Objetivos. En este estudio investigamos la expresión de 4 proteínas a través de inmunohistoquímica en 70 casos de carcinomas serosos de la TU (CSTU) (5 de bajo grado [BG], y 65 de alto grado [AG]) para determinar su papel pronóstico. Material y métodos. Se evaluó el estado de HER2/neu, p53, PAX8 y MIB-1 en matrices de tejidos, y se correlacionó con las siguientes variantes clinicopatológicas: edad, grado, metástasis ganglionares, estadio y supervivencia. Resultados. Demostramos la sobreexpresión de la oncoproteína HER2/neu en 20 de 65 (31%) CSTU AG. p53 se expresó en más de 50% (3+) del tumor en 59 (90,7%) casos, mientras que en 8 casos (12%), la expresión fue moderada o débil (2+). El PAX8 se expresó en 55 (78,5%) casos, y los otros 15 casos (21%) fueron negativos. El pronóstico de las pacientes cuyos tumores sobreexpresaron el HER2/neu fue más adverso (p=0,0001). p53, MIB-1 o PAX-8 no tuvieron un papel predictivo en el pronóstico de la enfermedad. Conclusiones. La relevancia del papel pronóstico de la sobreexpresión del HER2/neu en el CSTU, así como la posibilidad de seleccionar pacientes para recibir terapias dirigidas deben ser investigadas en más estudios (AU)
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Id: 155624
Autor: Cobo, Manuel; Gutiérrez, Vanesa; Rodelo, Luis; López, Omar; Ruiz, María; Godoy, Ana.
Título: Afatinib en pacientes con carcinoma escamoso de pulmón: contexto actual y opción de un tratamiento oral / Afatinib in patients with squamous cell carcinoma of the lung: current context and the option of oral treatment
Fonte: Med. clín (Ed. impr.);146(supl.1):25-29, abr. 2016. graf.
Idioma: es.
Resumo: El carcinoma escamoso de pulmón (SCC) representa un 30% del cáncer de pulmón de célula no pequeña (CPCNP). Docetaxel y el inhibidor de la tirosincinasa (ITK) del EGFR, erlotinib, han sido los 2 únicos fármacos aprobados para el tratamiento de segunda línea del SCC avanzado. La sobreexpresión de EGFR puede explicar la sensibilidad de SCC a ITK. Erlotinib demostró beneficio significativo en supervivencia global (SG) en líneas sucesivas en CPCNP, incluyendo histología escamosa. La magnitud de este beneficio es similar a la de la QT. Afatinib es un inhibidor irreversible de toda la familia ErbB (EGFR, HER2-4), que ha sido aprobado recientemente para su indicación actual, CPCNP avanzado con mutación de EGFR, y tiene una toxicidad básicamente gastrointestinal y cutánea, bien definida y manejable. El ensayo LUX-Lung 8 fue un estudio fase III aleatorizado en pacientes con CPCNP con histología escamosa en segunda línea, que comparó erlotinib frente a afatinib. Se incluyeron 795 pacientes y se observó beneficio significativo para afatinib en supervivencia libre de progresión (2,7 frente a 1,9 meses; HR: 0,79; IC del 95%, 0,68-0,91; p = 0,0012) y en SG (7,9 frente a 6,8 meses; HR: 0,81; IC del 95%, 0,69-0,95; p = 0,0077), así como mejoría significativa en SG a 12 y 18 meses. Se observó más diarrea y estomatitis con afatinib y más exantema con erlotinib, pero la proporción global de toxicidad fue similar en cada grupo. Afatinib ofreció mejores resultados en calidad de vida. En resumen, afatinib es una opción de tratamiento en segunda línea en CPCNP escamocelular sobre la base de los resultados de mejoría en supervivencia respecto a erlotinib (AU)

Squamous cell carcinoma (SCC) of the lung represents 30% of non-small cell lung cancers (NSCLC). Docetaxel and the EGFR tyrosine kinase inhibitor (TKI), erlotinib, are the only two drugs approved for second-line treatment of advanced SCC. The sensitivity of SCC to TKIs can be explained by EGFR overexpression. Erlotinib demonstrated a significant benefit in terms of overall survival (OS) in successive lines in NSCLC, including squamous histology. The magnitude of this benefit is similar to that of chemotherapy. Afatinib is an irreversible inhibitor of the entire ErbB family (EGFR, HER2-4) that has recently been approved for its current indication, advanced EGFR mutation-positive NSCLC and has well-defined and manageable toxicity, mainly gastrointestinal and cutaneous. The LUX-Lung 8 study was a phase III randomized trial in patients with NSCLC with squamous histology that compared erlotinib versus afatinib as second-line treatment. A total of 795 patients were included and a significant benefit was observed for afatinib in progression-free survival (2.7 vs 1.9 months (HR 0.79 [95%CI 0.68-0.91]; p=0.0012) and in OS (7.9 vs 6.8 months (HR 0.81 [95%CI 0.69-0.95]; p=0.0077), as well as a significant improvement in OS at 12 and 18 months. More diarrhoea and stomatitis was observed with afatinib and more rash with erlotinib, but the overall proportion of toxicity was similar in each group. Afatinib offered better results in quality of life. In summary, afatinib is a second-line treatment option in squamous NSCLC based on its survival advantage over erlotinib (AU)
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Id: 141572
Autor: Miranda Romero, Patricia; Marín Gil, Roberto.
Título: Trastuzumab emtansine in locally advanced or metastatic HER2 positive breast cancer; GENESIS-SEFH drug evaluation reporta / / Trastuzumab emtansina en cáncer de mama her2 positivo metastásico o localmente avanzado; informe de evaluación genesis-sefh
Fonte: Farm. hosp;39(3):171-175, mayo-jun. 2015. tab.
Idioma: en.
Resumo: Trastuzumab emtansina (T-DM1) is an antibody-drug conjugate directed against the HER2 for the treatment of HER2+ mestastatic breast cancer (MBC), who has previously received trastuzumab plus a taxane. According to the results of the EMILIA trial versus lapatinib plus capecitabine T-DM1 shows an improvement in progression-free survival (PFS) and the overall survival (OS). It has a favorable profile reducing the incidence of grade 3-4 adverse reactions such as hand-foot syndrome and diarrhea. On the contrary increases significantly severe thrombocytopenia; bleeding risk and liver function should also be monitored. With the current import price T-DM1 has a cost per QALY of over 120,000 Euros. The price of the drug for the Spanish NHS has not yet been established. Drug cost would be the key factor in the sensitivity analysis and a 50% reduction in the price of the drug would place it close to the threshold of cost-effectiveness usually considered in our midst. According to the budget impact model used, a maximum of 1,218 patients / year and the budgetary impact throughout the Spanish state would be at 70,490,850 Euros. In the initial analysis no advantage was found for T-DM1 in those patients without visceral involvement. Although a subsequent re-analysis of the results of PFS in which the definition of visceral involvement was specified a significant benefit was shown in this subgroup. We believe that this approach introduces a high degree of uncertainty, which does not guarantee the benefit achieved for this subgroup of patients (AU)

T-DM1 es un conjugado anticuerpo-fármaco dirigido contra el HER2 para el tratamiento del cáncer de mama metastásico (CMM) HER2 +, que ha recibido previamente trastuzumab más un taxano. De acuerdo con los resultados del ensayo EMILIA frente a lapatinib más capecitabina T-DM1 muestra una mejora en la supervivencia libre de progresión (SLP) y la supervivencia global (SG). Tiene un perfil favorable reducir la incidencia de reacciones adversas grado 3-4 tales como el síndrome mano-pie y la diarrea. Sin embargo, aumenta significativamente el riesgo de trombocitopenia grave y debe monitorizarse el riesgo de hemorragia y la función hepática. Con el precio de importación actual T-DM1 tiene un coste por AVAC de más de 120.000 Euros. El precio del fármaco para el Sistema Nacional de Salud en España aún no ha sido establecido. El precio del fármaco sería el factor clave en el análisis de sensibilidad y una reducción del 50% en el precio lo situaría cerca del umbral de coste-efectividad generalmente considerada en nuestro medio como aceptable. De acuerdo con el modelo de impacto presupuestario utilizado, se trataría un máximo de 1.218 pacientes / año y el impacto presupuestario de todo el estado español estaría entorno a 70.490.850 Euros para este volumen de pacientes. En el análisis inicial no se encontró ninguna ventaja para T-DM1 en aquellos pacientes sin afectación visceral. Aunque un re-análisis posterior de los resultados de SLP en el que se especifica la definición de la afectación visceral se muestra un beneficio significativo en este subgrupo. Creemos que este enfoque presenta un alto grado de incertidumbre, y no garantiza el beneficio logrado para este subgrupo de pacientes (AU)
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Id: 139875
Autor: Melé Olivé, Laura; Barrio Bernabé, Vanesa del; Bermejo Aycarr, Juan Ignacio; Blanco Gómez, I; Montesinos Sánchez-Girón, Olga.
Título: Carcinosarcoma mamario / Breast carcinosarma
Fonte: Prog. obstet. ginecol. (Ed. impr.);51(2):93-98, feb. 2008. ilus.
Idioma: es.
Resumo: El carcinosarcoma mamario es un tumor infrecuente y compuesto de una mezcla de tejido mesenquimal y zonas carcinomatosas epiteliales sin áreas de transición entre ambos componentes. Característicamente, y a diferencia del resto de carcinomas mamarios, suele expresar el gen EGFR y menos frecuentemente el HER-2. Estas neoplasias no responden al tratamiento hormonal y parcialmente al tratamiento quimioterápico convencional. Con todo, se están proyectando investigaciones para plantear nuevas líneas terapéuticas útiles para el tratamiento de uno de los carcinomas mamarios más agresivos conocidos (AU)

Breast carcinosarcoma is an infrequent tumor composed of a mixture of mesenchymal tissue and epithelial carcinomatous regions without transitional areas between the two components. Unlike other breast carcinomas, these tumors characteristically express the EGFR gene and, less frequently, the HER-2 gene. These neoplasms do not respond to hormone therapy and respond only partially to conventional chemotherapy. Research is being planned to find new and useful therapies for the treatment of carcinosarcoma, which is one of the most aggressive breast carcinomas known (AU)
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