RESUMEN
Background The genomic grade index (GGI) completes the prognostic value of histological grade (HG). Other proliferation markers include the mitotic activity index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in node-positive breast cancer (BC) patients treated with adjuvant anthracycline-based chemotherapy in the prospective PACS01 trial. Patients and methods The five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases and analysed as continuous values. We compared the correlations of each one with the other proliferation-related parameters and with histoclinical variables including the disease-free survival (DFS). Results Expected correlations were observed between the five parameters and for each parameter with biological features (hormone-receptor and HER2 status, molecular subtypes), but the GGI displayed the strongest correlations. The GGI outperformed the prognostic performance of the four other proliferation-related parameters for the DFS in all 204 patients and in the 95 HG2 patients. In multivariate analysis including the classical prognostic factors, only GGI remained significant. Finally, the GGI outperformed the prognostic performance of MKI67 mRNA expression in a series of 1599 samples and 656 HG2 cases. Conclusions In this small pilot biomarker study ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further validation is warranted in larger series.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Antígeno Ki-67/metabolismo , Índice Mitótico , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidad , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Estudios RetrospectivosRESUMEN
BACKGROUND: Prognosis of ovarian carcinoma is poor, heterogeneous, and not accurately predicted by histoclinical features. We analysed gene expression profiles of ovarian carcinomas to identify a multigene expression model associated with survival after platinum-based therapy. METHODS: Data from 401 ovarian carcinoma samples were analysed. The learning set included 35 cases profiled using whole-genome DNA chips. The validation set included 366 cases from five independent public data sets. RESULTS: Whole-genome unsupervised analysis could not distinguish poor from good prognosis samples. By supervised analysis, we built a seven-gene optimal prognostic model (OPM) out of 94 genes identified as associated with progression-free survival. Using the OPM, we could classify patients in two groups with different overall survival (OS) not only in the learning set, but also in the validation set. Five-year OS was 57 and 27% for the predicted 'Favourable' and 'Unfavourable' classes, respectively. In multivariate analysis, the OPM outperformed the individual current prognostic factors, both in the learning and the validation sets, and added independent prognostic information. CONCLUSION: We defined a seven-gene model associated with outcome in 401 ovarian carcinomas. Prospective studies are warranted to confirm its prognostic value, and explore its potential ability for better tailoring systemic therapies in advanced-stage tumours.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Carcinoma/diagnóstico , Carcinoma/tratamiento farmacológico , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/tratamiento farmacológico , Compuestos de Platino/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores Farmacológicos/análisis , Biomarcadores de Tumor/análisis , Carcinoma/genética , Carcinoma/mortalidad , Técnicas de Apoyo para la Decisión , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes Relacionados con las Neoplasias/fisiología , Humanos , Análisis por Micromatrices , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Compuestos de Platino/administración & dosificación , Pronóstico , Resultado del TratamientoRESUMEN
Basal-like carcinomas represent 10 to 15% of invasive breast carcinomas and have been identified from gene expression studies. Morphologically, these tumors are undifferentiated histopronostic grade 3 carcinomas, identified in clinical practice according to their immunophenotype "triple zero" (estrogen, progesterone and ERBB2 negative) associated with the high molecular weight cytokeratins 5/6/14 and/or EGFR expression. At the molecular level, these tumors harbour nearly 100% P53 mutations, a high rate of PTEN mutations with an AKT pathway's activation and numerous chromosomal alterations such as gains and losses. They share a high degree of similarity at the morphological, phenotypical and molecular level with BRCA1 tumors that justify the proposal of a different name such as "triple zero/BRCA1 like" carcinomas for sporadic basal-like carcinomas. Indeed, the current "basal-like" name could suggest a myoepithelial cellular origin of such lesions. Furthermore, tumors with such a basal-like immunophenotype constitute a heterogeneous group of tumors encompassing good prognosis tumors such as adenoid cystic and juvenile secretory carcinomas. There is an urgent need for more specific therapies for basal-like/triple zero/BRCA1-like tumors. Therapeutic progresses rely on a better understanding of the molecular alterations that occur in these tumors and the BRCA1 tumors. Indeed, recent clinical trials with PARP inhibitors for basal-like/BRCA1 like tumors should improve the prognosis of these patients and are a direct benefit of a better understanding of the molecular biology of these tumors.
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Neoplasias de la Mama/genética , Carcinoma Basocelular/genética , Perfilación de la Expresión Génica/métodos , Genes BRCA1 , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Femenino , Silenciador del Gen , Genes p53/genética , Humanos , Mutación/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fenotipo , Pronóstico , Terminología como AsuntoRESUMEN
BACKGROUND: Several authors reported sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NC). Nevertheless, the ideal time of SLNB is still a matter of debate. METHODS: We evaluated the feasibility and the accuracy of SLNB before NC using a combined procedure (blue dye and radio-labelled detection) before NC. Axillary lymph node dissection (ALND) was performed after completion of NC in a homogeneous cohort study with clinically axillary node-negative breast cancer. RESULTS: Among the 20 women who had metastatic SLNB (65%), 4 (20%) had additional metastatic node on ALND. By contrast, all the 11 women who had no metastatic SLNB had no involved nodes in the ALND. The SLN identification rate before NC was 100% with any false negative. CONCLUSIONS: SLNB before NC is a feasible and an accurate diagnostic tool to predict the pre-therapeutic axilla status. These findings suggest that ALND may be avoided in patients with a negative SLNB performed before NC.
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Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Estudios de Factibilidad , Femenino , Francia , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
PURPOSE: Predictive factors of non-sentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) have been studied in the case of sentinel node (SN) involvement, with validation of a nomogram. This nomogram is not accurate for SN micrometastasis. The purpose of our study was to determine a nomogram for predicting the likelihood of NSN involvement in breast cancer patients with a SN micrometastasis. METHODS: We collated 909 observations of SN micrometastases with additional ALND. Characteristics of the patients, tumours and SN were analysed. RESULTS: Involvement of SN was diagnosed 490 times (53.9%) with standard staining (HES) and 419 times solely on immunohistochemical analysis (IHC) (46.1%). NSN invasion was observed in 114 patients (12.5%), whereas 62.3% (71) had only one NSN involved and 37.7% (43) two or more NSN involved. In multivariate analysis, significant predictive factors were: tumour size (pT stage < or = 10 mm or >11 and < or = 20 or >20 mm [odds ratio (OR) 2.1 and 3.43], micrometastases detected by HES or IHC [OR 1.64], presence or absence of lymphovascular invasion (LVI) [OR 1.76], tumour histological type mixed or not [OR 2.64]. The rate and probability of NSN involvement with the model are given for 24 groups, with a representation by a nomogram. CONCLUSION: One group, corresponding to 10.1% of the patients, was associated with a risk of NSN involvement of less than 5%, and five groups, corresponding to 29.8% of the patients, were associated with a risk < or = 10%. Omission of ALND could be proposed with minimal risk for a low probability of NSN involvement.
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Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Nomogramas , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Modelos Biológicos , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Breast conserving surgery and mastectomy are equivalent for overall survival. However, the rate of local recurrence is higher for breast conserving surgery. Several predictive factors for local recurrence have been identified and some of them such as margins of resection, radiation therapy, chemotherapy, and hormonotherapy can be modified. The aim of this study is to review arguments in the literature to define optimal margins of resection. The orientation of the specimen and the inking of lateral margins are essentials for the histopathological analysis. Lateral margins are the most important since the resection is close to the pectoral muscle. According to the literature, the rate of local recurrence is higher when margins are positive. Moreover, the presence of tumoral cells on specimen after a re-excision is correlated with the positivity of the margins. There are no agreements about the number of millimeters requested to consider a margin sufficient. However, two millimeters seem to show a decrease of local recurrence. The influence of extensive intraductal component on local recurrence risk has been studied. Several factors are correlated and to define independent factors seem to be interesting.
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Neoplasias de la Mama/cirugía , Carcinoma in Situ/cirugía , Carcinoma Ductal de Mama/cirugía , Neoplasias de la Mama/patología , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Recurrencia Local de Neoplasia/prevención & control , Neoplasia Residual , PronósticoRESUMEN
Invasive ductal carcinomas (IDCs) and invasive lobular carcinomas (ILCs) are the two major pathological types of breast cancer. Epidemiological and histoclinical data suggest biological differences, but little is known about the molecular alterations involved in ILCs. We undertook a comparative large-scale study by both array-compared genomic hybridization and cDNA microarray of a set of 50 breast tumors (21 classic ILCs and 29 IDCs) selected on homogeneous histoclinical criteria. Results were validated on independent tumor sets, as well as by quantitative RT-PCR. ILCs and IDCs presented differences at both the genomic and expression levels with ILCs being less rearranged and heterogeneous than IDCs. Supervised analysis defined a 75-BACs signature discriminating accurately ILCs from IDCs. Expression profiles identified two subgroups of ILCs: typical ILCs ( approximately 50%), which were homogeneous and displayed a normal-like molecular pattern, and atypical ILCs, more heterogeneous with features intermediate between ILCs and IDCs. Supervised analysis identified a 75-gene expression signature that discriminated ILCs from IDCs, with many genes involved in cell adhesion, motility, apoptosis, protein folding, extracellular matrix and protein phosphorylation. Although ILCs and IDCs share common alterations, our data show that ILCs and IDCs could be distinguished on the basis of their genomic and expression profiles suggesting that they evolve along distinct genetic pathways.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Antígenos CD , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Cromosomas Artificiales Bacterianos , Femenino , Humanos , Mutación/genética , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína p53 Supresora de Tumor/genéticaRESUMEN
AIMS: To assess the impact of cytokeratin (CK) 5/6 and E-cadherin immunohistochemistry on diagnostic agreement of non-invasive proliferative breast lesions. METHODS AND RESULTS: Twenty pathologists classified 105 cases of non-invasive proliferative breast lesions into 10 diagnostic categories. One haematoxylin and eosin (H&E) slide of each case was analysed on a first round and one H&E slide with corresponding CK5/6 and E-cadherin immunohistochemistry was analysed on a second round. Interobserver reproducibility for category-specific and management-specific lesions was measured on each round. CK5/6 and E-cadherin had little impact on diagnostic agreement, which remained moderate between the first and second rounds (overall kappa coefficients of 0.47 and 0.53, respectively, P = NS). Levels of agreement slightly improved for lesions with specific CK5/6 and E-cadherin immunoprofiles (usual ductal hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, non-high-grade ductal carcinoma in situ), but the differences observed were not statistically significant. However, diagnostic agreement improved when lesions were grouped according to their management category (overall kappa coefficients of 0.58 and 0.66 in the first and second rounds, respectively). CONCLUSIONS: CK5/6 and E-cadherin immunohistochemistry has little impact on interobserver reproducibility for non-invasive breast lesions. Diagnostic agreement can, however, be improved by grouping lesions in management categories.
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Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Mama/patología , Cadherinas/análisis , Carcinoma Intraductal no Infiltrante/diagnóstico , Queratinas/análisis , Biomarcadores de Tumor/inmunología , Neoplasias de la Mama/patología , Cadherinas/inmunología , Carcinoma Intraductal no Infiltrante/patología , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia , Inmunohistoquímica , Queratinas/inmunologíaRESUMEN
OBJECTIVES: To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy. METHODS: One hundred and forty-four patients with biopsy-proven stage IB-IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status. RESULTS: Tumour FIGO stages were IB-II in 91 cases and III-IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB-II and III-IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1-67.5] and 65% [95% CI: 56.2-75]. OS was significantly affected by the type of surgery (p<2.10(-16)), the presence of tumoural residue (p=0.002) and the pelvic lymphatic status (p<0.001). DFS was affected by the pelvic (p=0.02) and para-aortic lymphatic status (p=0.009). No significant difference was observed between OS and DFS in stage IB-II and III-IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases (p=0.022). CONCLUSION: Survival rates were equivalent between patients with IB-II and III-IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.
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Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Radioterapia , Análisis de Supervivencia , Neoplasias del Cuello Uterino/patologíaRESUMEN
Breast cancers that overexpress the ERBB2 tyrosine kinase receptor may be treated with the recombinant humanized monoclonal anti-ERBB2 antibody trastuzumab (herceptin). However, resistance to this targeted therapy is frequent. We have determined the response of 18 breast tumor cell lines to trastuzumab and compared it with the ERBB2 phosphorylation status using antibodies directed against tyrosine residue 1248. We show that sensitivity to trastuzumab is frequently associated with the expression of a phosphorylated ERBB2 protein.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos/fisiología , Receptor ErbB-2/metabolismo , Anticuerpos Monoclonales Humanizados , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Femenino , Marcación de Gen , Humanos , Fosforilación , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , TrastuzumabRESUMEN
Inflammatory breast carcinoma (IBC) is a rare but aggressive tumour associated with poor outcome owing to early metastases. Increased expression of c-Met protein correlates with reduced survival and high metastatic risk in human cancers including breast carcinomas and is targetable by specific drugs, that could potentially improve the prognosis. In the present study, we compared c-Met expression in IBC (n=41) and non-IBC (n=480) immunohistochemically (Ventana Benchmark autostainer) in two tissue microarrays (TMA) along with PI3K and E-cadherin. The results were quantified through an automated image analysis device (SAMBA Technologies). We observed that (i) c-Met was significantly overexpressed in IBC as compared with non-IBC (P<0.001), (ii) PI3K was overexpressed (P<0.001) in IBC, suggesting that the overexpressed c-Met is functionally active at least through the PI3K signal transduction pathway; and (iii) E-cadherin was paradoxically also overexpressed in IBC. We concluded that overexpressed c-Met in IBC constitutes a potential target for specific therapy for the management of patients with poor-outcome tumours such as IBC. Automated image analysis of TMA proved to be a valuable tool for high-throughput immunohistochemical quantification of the expression of intratumorous protein markers.
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Neoplasias de la Mama/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Análisis de Matrices Tisulares , Automatización , Cadherinas/metabolismo , Inmunohistoquímica , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.
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Ácido Anhídrido Hidrolasas/genética , Neoplasias de la Mama/genética , Rotura Cromosómica , Cinesinas/genética , Miosinas/genética , Proteínas de Neoplasias/genética , Ubiquitina-Proteína Ligasas/genética , Ácido Anhídrido Hidrolasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Sitios Frágiles del Cromosoma , Cromosomas Humanos Par 6/genética , Femenino , Técnica del Anticuerpo Fluorescente , Genes Supresores de Tumor , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Cinesinas/metabolismo , MicroARNs , Persona de Mediana Edad , Miosinas/metabolismo , Invasividad Neoplásica/patología , Proteínas de Neoplasias/metabolismo , Pronóstico , Interferencia de ARN , Tasa de Supervivencia , Análisis de Matrices Tisulares , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
AIM: To report the outcome of 30 patients who underwent surgery after concomitant chemoradiation for locally advanced cervical cancer with residual disease > or = 2 cm. METHODS: From 1988 to 2004, 143 patients with FIGO stage IB2-IVA cervical cancer underwent surgery after concurrent chemoradiotherapy. Among them, 30 had a residual cervical tumour > or = 2 cm prior to surgery. Surgery consisted in a simple or radical hysterectomy (n=15) or in a pelvic exenteration (n=15). Endpoints were recurrence and distant metastasis rates, overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Analysis included FIGO stage, response to chemoradiation, para-aortic lymphatic status or type of surgery: palliative (remaining disease after surgery) or curative (no evidence of remaining disease after surgery). RESULTS: Surgery has been only palliative in 11 cases. Pelvic recurrences occurred in 8 patients after a median interval of 8.8 months. Distant metastases occurred in 8 patients after a median interval of 13 months. So far, 16 patients have died (53.3%). The 3-year and 5-year OS rates are 64.9% and 55.6%, respectively, for the 19 patients who had a curative surgery. The DFS rate is 50.8% at 3 and 5 years in this latter group. Overall 12 patients (40%) are alive and free of disease after a median follow-up of 32.5 months. CONCLUSIONS: Adjuvant surgery may improve the outcome of patients with bulky residual tumour after chemoradiation for locally advanced cervical cancer, allowing a 5-year OS of 55.6% after curative intervention.
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Neoplasia Residual/cirugía , Neoplasias del Cuello Uterino/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Distribución de Chi-Cuadrado , Terapia Combinada , Femenino , Humanos , Histerectomía , Modelos Logísticos , Metástasis Linfática , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/radioterapia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
Standard treatment of locally advanced cervical carcinoma is actually represented by concomitant chemoradiotherapy followed by brachytherapy since several randomised study results in 1999. Surgical resection after concomitant chemoradiotherapy for locally advanced cervical carcinoma is discussed without evidence of benefice on survival and because morbidity. The aim of this study is to discuss surgery after chemoradiotherapy in terms of rate of morbidity and residual tumor, rate of pelvic disease control, overall survival and disease-free survival.
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Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/cirugía , Braquiterapia , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/radioterapiaRESUMEN
PURPOSE: The aim of this study is to show that the removal of the rectum is not an obstacle to implement an optimal surgery in advanced epithelial cancer of the ovary. MATERIAL AND METHODS: Retrospective study on a population of 44 women with advanced epithelial cancer of the ovary. The surgery was realized between January 95 and July 03, and all surgeries required a posterior exenteration. This treatment was completed by chemotherapy for 36 of them. RESULTS: The median survival of this population is 36.6 months. 6/44 patients (13.6%) had post-operative complications. The completion of chemotherapy started after an average of 5.2 weeks after surgery. All the assessable patients (43/44) have an anal satisfactory continence. CONCLUSION: The posterior exenteration, when it's necessary, for advanced epithelial cancer of the ovary must not be an obstacle to obtain an optimal surgery. Anal continence is respected and there are no more complications. This surgical act is safe for the management of this pathology without delaying the others therapeutics and allowing a satisfactory quality of life.
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Adenocarcinoma/cirugía , Carcinoma Endometrioide/cirugía , Carcinosarcoma/cirugía , Colon/cirugía , Neoplasias Ováricas/cirugía , Exenteración Pélvica , Recto/cirugía , Adenocarcinoma/patología , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/cirugía , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Carcinoma Endometrioide/patología , Carcinosarcoma/patología , Colostomía , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/cirugía , Cistectomía , Estudios de Factibilidad , Femenino , Humanos , Histerectomía , Ileostomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Ovario/patología , Cuidados Preoperatorios , Calidad de Vida , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; P<0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.
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Proteínas Sanguíneas/análisis , Neoplasias de la Mama/tratamiento farmacológico , Proteómica , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Periodo Posoperatorio , Pronóstico , Análisis por Matrices de Proteínas , RecurrenciaRESUMEN
A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Basocelular/metabolismo , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/clasificación , Carcinoma Basocelular/genética , Carcinoma Basocelular/patología , Células Epiteliales , Femenino , Genes erbB-2/fisiología , Humanos , Técnicas para Inmunoenzimas , Mesodermo/metabolismo , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
BACKGROUND: ERBB2 overexpression predicts a worse outcome for patients receiving high-dose chemotherapy (HDC). Trastuzumab improves response rate and survival in ERBB2 overexpressing metastatic breast cancer patients (MBC). We investigated the feasibility of combining high-dose alkylating agents with autologous hematopoietic stem cell (AHSC) support and trastuzumab in ERBB2 overexpressing MBC. PATIENTS AND METHODS: Eleven consecutive patients with pre-treated ERBB2 overexpressing MBC were enrolled. HDC regimen consisted of a single course of cyclophosphamide 120 mg/kg + melphalan 140 mg/m2 (CyMEL, n =8), a single course of Thiotepa 600 mg/m2 (TTP, n = 1) or a sequential combination of Thiotepa 600 mg/m2 followed on day 21 by BCNU 600 mg/m2 (TTP-BCNU, n =2). Trastuzumab (4mg/kg) was started 24 h after AHSC infusion and then administered weekly (2 mg/kg). RESULTS: Median time to neutrophil and platelet recovery was 10 and 14.5 days, respectively. Three patients experienced febrile neutropenia and in 2 Herpes virus infections were documented. Five grade III/IV mucositis/oesophagitis were recorded. One patient experienced a reversible atrial arrhythmia on day 2 of trastuzumab, and another patients had a nonsymptomatic decrease in LVEF >10% on week 12 of trastuzumab. No toxic death was recorded. Median time to progression was 5 months (1 to 38 +). CONCLUSION: Combining alkylating agent-based HDC and trastuzumab appears to be feasible in ERBB2 overexpressing MBC and warrants further investigation in a larger cohort.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Receptor ErbB-2/biosíntesis , Trasplante de Células Madre , Adulto , Anticuerpos Monoclonales Humanizados , Plaquetas/metabolismo , Terapia Combinada , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Corazón/efectos de los fármacos , Humanos , Melfalán/administración & dosificación , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutrófilos/metabolismo , Riesgo , Factores de Tiempo , TrastuzumabRESUMEN
PURPOSE: The aim of this study was to define the interest of sentinel lymph node biopsy (SLNB) for the staging of ductal carcinoma in situ (DCIS) and DCIS with micro-invasion (DCISM) in patients with breast carcinoma. MATERIAL AND METHODS: From June 1999 to December 2002 we listed, in a retrospective study, 52 patients treated surgically for a DCIS or a DCISM. All except one had an histology before surgery, and all had SLNB. Intraoperative imprint cytology of the sentinel lymph node (SLN) was performed then there were analysed by staining with hematoxylin-eosin. Patients with positive SLN underwent complete axillary dissection. RESULTS: It was removed an average of three SLNs by patient (extreme 1 to 6). Metastases in the SLN were detected in four (7,7%) of the 52 patients, including three cases had only micrometastases in the SLN. In the four patients treated with complete axillary dissection, the SLN were the only positives nodes. CONCLUSION: The SLNB for DCIS and DCISM increases the involvement rate of lymph node. Because of the widespread for early detection of breast cancer, it is noted a regular increase in the rate of DCIS. Even if the attitude to be had towards the lymph node metastases in these cases is not yet well defined, and so only 2% of the patients approximately die of this pathology, it is interesting because of increase in absolute value of mortality, to try to improve the prognosis criteria to modify the treatment of this pathology.
Asunto(s)
Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Biopsia del Ganglio Linfático Centinela , Femenino , Humanos , Invasividad Neoplásica , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
AIMS: The objectives of this study were to compare the postoperative morbidity of Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) and to compare the views of surgeons and patients regarding postoperative morbidity. METHODS: A prospective and comparative study was initiated to evaluate, 1 year after surgery, morbidity and sequelae after SLNB in 231 patients. Group I (n=141) underwent SLNB without ALND, group II (n=90) underwent SLNB followed by ALND when SLN where involved. Morbidity analysis was performed, respectively, by surgeons and patients. RESULTS: One hundred and eighty-five patients (80.5%) completed the questionnaire including 113 with SLNB alone, and 72 with ALND. One year after surgery, SLNB produced less morbidity than ALND for symptoms and function. There were significantly different assessments between surgeons and patients for pain, arm mobility and sensitiveness. CONCLUSIONS: One-year postoperative morbidity after SLNB is significantly lower than after ALND but views of surgeons and patients appears to be significantly different. Additional data are required to assess late consequences of axillary surgery.