RESUMEN
BACKGROUND: When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion. METHODS: The SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed. RESULTS: From May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56-77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion. CONCLUSIONS: Underestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy.
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Neoplasias de la Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Axila , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Femenino , Humanos , Ganglios Linfáticos/cirugía , Mastectomía , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Prospectivos , Receptor ErbB-2/análisis , Análisis de Matrices Tisulares , Procedimientos Innecesarios , Adulto JovenRESUMEN
PURPOSE: Some children with extracranial germ cell tumors (GCT) relapse after or do not respond to first-line treatment combining chemotherapy and surgery, of whom very few experience long-term survival despite multimodal salvage treatment. METHODS: This prospective study, part of the French TGM95 Protocol for non-seminomatous GCT (NSGCT), included 19 (7%) children with malignant refractory or recurrent extracranial NSGCT who were studied to identify prognostic factors and determine the best salvage treatment. RESULTS: At the end of the first-line treatment, 10 and 9 children were in complete and incomplete remission, respectively. Events occurred within 2 years (5-23 months) after initial diagnosis. A progression was observed in 13 patients at least in one site initially involved. Two patients had a purely biological relapse (increase in isolated markers), and four patients had a purely metastatic relapse (brain location in three cases). After salvage treatment combining surgery and various types of chemotherapy (including high-dose chemotherapy (HDCT) in 10 cases), the 5-year event-free survival and overall survival rates were of 26% (95%CI: 9.6-46.8%) and 32% (95%CI: 12.9-52.2%), respectively. Patients who underwent complete surgery (or without any detectable tumor) had higher survival rate than patients who underwent partial surgery or for whom surgery was not feasible (P = 0.0003) at first relapse while this rate was similar between patients treated or not with HDCT. CONCLUSION: In pediatric recurrent or refractory NSGCT, complete excision of the tumor appears essential. The role of HDCT remains debated.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Bleomicina/administración & dosificación , Niño , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Lactante , Metástasis Linfática , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/patología , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Neoplasias Testiculares , Vinblastina/administración & dosificación , Adulto JovenRESUMEN
The aim of this study was to prospectively evaluate the predictive value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG-PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV(max)). Pts were classified as non-responders (NR) when the decrease of SUV(max) in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV(max) decrease according to histological response was -52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Terapia Neoadyuvante , Tomografía de Emisión de Positrones , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Insuficiencia del TratamientoRESUMEN
The incidence of leptomeningeal metastases (LM) in patients with breast cancer (BC) is increasing as a result of increased screening and improved patient survival. However, the median survival time after diagnosis of LM is between 5 weeks (without any treatment) and 5 months (for aggressively treated patients). In an attempt to identify clinicopathological risk factors for LM, we carried out a case-control study of 100 women with BC. Fifty patients with BC and LM were enrolled and an additional 50 patients with BC and no CNS metastases including leptomeningeal spread were selected as controls. Patients who had developed LM were selected between December 2006 and August 2008. The control group was matched for: age at diagnosis, year of diagnosis, and initiation of chemotherapy at BC diagnosis. The ILC type (P = 0.03), ER-negative (P = 0.01) and PR-negative status (P = 0.03), and initial M+ status at BC diagnosis (P = 0.008) tended to be more frequent in LM patients. These characteristics should lead to early appropriate assessments being performed in this targeted population when a neurological complaint appears, in order to detect LM as soon as possible.
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Neoplasias de la Mama/patología , Neoplasias Meníngeas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Neoplasias Óseas/secundario , Neoplasias de la Mama/mortalidad , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Neoplasias Meníngeas/mortalidad , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Parvovirus H-1 (H-1 PV) preferentially replicates in malignant cells resulting in their death by cytolysis. It has often been considered a potential candidate for use in novel anticancer therapy. To evaluate its potential in a model of natural tumors, we assayed in vitro the effect exerted by H-1 PV on short-term cultures derived from breast tumor samples freshly excised from patients. Our results show that H-1 PV effectively kills tumor-derived cells, whereas normal tissue-derived cells showed no H-1 PV-induced cytopathic effects (CPE). We also determined that the H-1 PV sensitivity (up to 67% sensitive cultures) is related with the quantities of virus assayed. We further examined the expression and phosphorylation state of the parvoviral nonstructural protein 1 (NS1), known to be associated with parvoviruses-induced CPE. Both appear to be impaired in normal tissue-derived cells and resistant cultures. Finally, we show that H-1 PV sensitivity in cultures correlates significantly with higher tumor grades (Nottingham combined histologic grade 2 or 3). This report confirms that H-1 PV can efficiently induce CPE in primary breast tumor cells in vitro. It identifies tumor characteristics representing potential criteria for recruiting patients for clinical evaluation of H-1 PV antitumor effects.
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Neoplasias de la Mama/virología , Parvovirus H-1 , Viroterapia Oncolítica/métodos , Animales , Western Blotting , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Células Cultivadas , Femenino , Células HeLa , Humanos , Ratones , Ratones SCID , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of this study was to compare the complete pathologic response (CPR) rate in 56 nonmetastatic inflammatory breast cancer patients according to the classification used and to look for a correlation between the CPR and overall survival. Initial biopsies and mastectomy specimens were reviewed by the same pathologist. The clinical response rate was 75%. A CPR was observed in 11 cases according to Sataloff, three according to Chevallier and five according to the NSABP. There was no correlation between the clinical and pathologic responses and none of them was predictive of relapse free survival or overall survival. We propose a standardization of the pathologic process of the mastectomy specimens so that a CPR has a clear definition across the institutions, with a good reproducibility whatever the classification used.
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Antineoplásicos/uso terapéutico , Neoplasias Inflamatorias de la Mama/tratamiento farmacológico , Neoplasias Inflamatorias de la Mama/patología , Recurrencia Local de Neoplasia , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Resultado del TratamientoRESUMEN
In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS' guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs).
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Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Receptor ErbB-2/análisis , Francia , Humanos , Inmunohistoquímica/normas , Hibridación in Situ/normas , Control de Calidad , RegistrosRESUMEN
PURPOSE: The MammoSite is a device that was developed with the goal of making breast-conserving surgery (BCT) more widely available. Our objective was to evaluate the MammoSite device performances after an open cavity placement procedure and quality of life in highly selected patients with early-stage breast cancer. METHODS AND MATERIALS: From March 2003 to March 2005, 43 patients with T1 breast cancer were enrolled in a phase II study. The median age was 72 years. Twenty-five (58%) patients were treated with high-dose rate brachytherapy using the MammoSite applicator to deliver 34Gy in 10 fractions. The main disqualifying factor was pathologic sentinel node involvement (10/43; 23%). There were no device malfunctions, migration or rupture of the balloon. RESULTS: After a median follow-up of 13 months, there were no local recurrences and one contralateral lobular carcinoma. Seventeen (68%), 13 (52%), 8 (32%), 5 (20%) and 2 (8%) patients had erythema, seroma, inflammation, hematoma and sever infection, respectively. Only 2 patients developed telangiectasia. At 1 year the rate of "good to excellent" cosmetic results was 84%. Significant changes in QoL were observed for emotional and social well-being between 3 and 12 months. At 24 months, only emotional well-being subscore changes were statistically significant (p=0.015). CONCLUSIONS: Our data in patients older than 60 years support the previously published data. Histologic features were the main disqualifying criteria. With higher skin spacing levels we observed very low incidence of telangiectasia. QoL evaluation indicates that baseline scores were satisfactory. Changes concerned emotional and social well-being.
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Braquiterapia/métodos , Neoplasias de la Mama/radioterapia , Cateterismo , Calidad de Vida , Anciano , Braquiterapia/efectos adversos , Braquiterapia/instrumentación , Neoplasias de la Mama/patología , Fraccionamiento de la Dosis de Radiación , Estética , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Satisfacción del Paciente , Biopsia del Ganglio Linfático Centinela , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
PURPOSE: Leptin and obesity are clearly related, and obesity is associated with an increased risk of breast cancer. We therefore measured the expression of leptin and its two main receptor isoforms, OBR-L and OBR-S, in 322 breast cancers. We analyzed their relations with the classical prognostic factors and with survival to establish their links with breast cancer. EXPERIMENTAL DESIGN: The expression of leptin and its receptors was quantified by real-time reverse transcription-PCR, using TaqMan fluorogenic probes and an ABI PRISM 7700 sequence detector system (Applied Biosystems, Courtaboeuf, France). TATA box binding protein was used to normalize expression. The human breast cancer cell, SK-BR-3, expressing the three targets, was chosen as the calibrator sample (i.e., target expression = 1). RESULTS: All the tumors expressed both receptors, and 318 of 322 expressed leptin. These three variables correlated positively with each other and with estradiol and progesterone receptors, whereas they correlated negatively with histoprognostic grading and tumor diameter. OBR-L/OBR-S expression was inversely correlated with progesterone receptors. Patients with elevated OBR-S expression had longer relapse-free survival (P = 0.008), whereas high OBR-L/OBR-S was associated with a shorter relapse-free survival (P = 0.05). In Cox multivariate analyses, OBR-S maintained its prognostic value (P = 0.02; relative risk, 0.51). CONCLUSIONS: This study shows that (a) almost all of the breast cancers coexpress leptin and its two main isoforms of receptors, suggesting that the human epithelial breast cancer cells respond to leptin acting via an autocrine pathway; (b) high expression levels of leptin and leptin receptors are biological markers of a more differentiated phenotype; and that (c) OBR-S is an independent prognostic factor.
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Neoplasias de la Mama/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Leptina/genética , ARN Mensajero/biosíntesis , Receptores de Superficie Celular/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Fenotipo , Pronóstico , ARN Mensajero/genética , ARN Mensajero/aislamiento & purificación , Receptores de Leptina , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de SupervivenciaRESUMEN
Tumor blood vessels participate in the immune response against cancer cells and we previously used pre-clinical models to demonstrate that egfl7 (VE-statin) promotes tumor cell evasion from the immune system by repressing endothelial cell activation, preventing immune cells from entering the tumor mass. In the present study, the expression levels of egfl7 and that of ICAM-1 as a marker of endothelium activation, were evaluated in peritumoral vessels of human breast cancer samples. Breast cancer samples (174 invasive and 30 in situ) from 204 patients treated in 2005 were immunostained for CD31, ICAM-1 and stained for egfl7 using in situ hybridization. The expression levels of ICAM-1 and egfl7 were assessed in peritumoral areas using semi-quantitative scales. There was a strong and significant inverse correlation between the expression of ICAM-1 and that of egfl7 in CD31+ blood vessels. When the ICAM-1 score increased, the egfl7 score reduced significantly (P=0.004), and vice-versa (Cuzick's test for trend across ordered groups). In order to determine which gene influenced the other gene between egfl7 and ICAM-1, the expression levels of either gene were modulated in endothelial cells. Egfl7 regulated ICAM-1 expression while ICAM-1 had no effects on egfl7 expression in the same conditions. Altogether, these results provide further results that egfl7 serves a regulatory role in endothelial cell activation in relation to immune infiltration and that it is a potential therapeutic target to consider for improving anticancer immunotherapies.
RESUMEN
Twenty-seven patients with recurrent soft-tissue sarcoma (STS) entered a multicenter study to determine the efficacy of the combination paclitaxel 200 mg/m and epirubicin 75 mg/m administered every 21 days. Patient characteristics included the following: 14 women and 13 men, median age of 52 years, 12 patients had local recurrence and 20 had metastasis. Eighteen patients had previously received chemotherapy for recurrent disease. The main grade III to IV hematologic toxicities were neutropenia (70%), anemia (3.7%), and thrombocytopenia (7.4%). Febrile neutropenia occurred in 5 patients (18.5%). Severe nonhematologic toxicities were rare. Two patients had a partial response (7.4%; 95% CI: 2.6-12.2%), with a median response duration of 3 and 5 months. Six patients had stable disease (22.2%), and 19 had progressive disease (70.5%). The median overall survival from study inclusion was 8 months. This study suggests the association paclitaxel-epirubicin does not increase the known activity of anthracycline in recurrent STS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Terapia Recuperativa , Sarcoma/secundario , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To perform sentinel node with local anaesthesia in the breast carcinoma without frozen section. So we used definitive histological and immunohistochemical results of sentinel node the day of conserving surgery with complete axillary lymph node dissection under general anaesthesia in case of involved nodes. METHODS: Patients with a stage TNM > T1 or N1, a multicentric breast cancer, a neoadjuvant chemotherapy, an allergy, an obesity or no detection of hot sentinel node were excluded. Patients in ambulatory surgery had scintigraphy 3 hours after injection of radiotracer. If we had a hot sentinel node, we applied Emla 5% cream on the areolar and axillary site and gave midazolam. We performed an intradermal injection of 2 ml of xylocaine with adrenaline above cancer and in the subareolar site in case of non-palpable cancer. With the same needle, we injected 2 ml of blue dye. We injected so 2 ml of xylocaine with adrenaline in the axillary hot spot. We completed local anaesthesia with 16 ml of xylocaine with adrenaline step by step on the route that intraoperative gamma probe showed us. RESULTS: We performed 17 patients (52.6 years [38-62]; body mass index = 23.7 [20-34.1], size of tumour = 10.8 mm [1-25]). We detected 100% of sentinel node. We had a secondary haematoma which was evacuated. CONCLUSION: Perform sentinel node under local anaesthesia is possible for patients with no obesity but radio tracer is absolutely necessary.
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Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela/métodos , Adulto , Anestésicos Locales , Axila , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias/métodosRESUMEN
Little is known about epidemiology of adults soft tissue and visceral sarcomas (ASTS). The frequency of previous cancers and associated genetic diseases has been analyzed out of 493 ASTS, treated between 1997 and 2002 at Oscar Lambret Cancer Center. Median age is 51, sex ratio is close to 1. Liposarcomas and malignant fibrous histiocytofibromas are the two main types (respectively 104 and 86 cases). Upper and lower limbs are the two main locations (respectively 176 and 75 cases). Fifteen patients had associated genetic disease, including 12 cases of Recklinghausen diseases. 7 out of those 15 patients have neurosarcoma. 30 patients have previous cancers, including 7 breast cancers, 3 lymphomas and 3 chronic lymphocytic leukemias. Four out of those 30 patients have two different previous cancers. 13 patients have radiation-induced sarcomas, after an average 10-year-period, and an average dose of 53 Gy. Undifferenciated sarcomas are the main histologic type (8/13), followed by angiosarcomas (2/13). Radiation-induced sarcomas are located in the chest wall (7/13), in pelvis (2/13) and head and neck (2/13). Those sarcomas are high grade (10 grade III tumours). ASTS epidemiology is complex with different risk factors depending on histologic type.
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Enfermedades Genéticas Congénitas/epidemiología , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Sarcoma/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Enfermedades Genéticas Congénitas/complicaciones , Histiocitoma Fibroso Benigno/epidemiología , Humanos , Liposarcoma/epidemiología , Masculino , Persona de Mediana Edad , Sarcoma/genética , Sarcoma/patologíaRESUMEN
Egfl7 (VE-statin) is specifically expressed by endothelial cells of normal tissues but its expression is deregulated in human cancers. Analysis of expression of Egfl7 protein and transcripts in 211 human breast cancer samples shows that Egfl7 is strongly expressed by breast tumor cells. Egfl7 expression is significantly higher in invasive ductal than in invasive lobular carcinoma. Expression of Egfl7 transcripts is also higher in lower SBR grade lesions and in lesions which are not associated with lymph node invasion. Within the invasive ductal carcinoma sub-population, expression of Egfl7 transcripts is correlated with the SBR score and with the ER+ status. High transcript and Egfl7 protein levels significantly correlate with the absence of axillary lymph node invasion. In lymph nodes, the levels of Egfl7 are correlated with the histological type of the primary lesions; they are higher in ductal than in lobular carcinoma. Egfl7 expression is thus associated with better prognosis factors and with the absence of lymph node invasion in human breast cancer lesions.
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Neoplasias de la Mama Masculina/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Lobular/metabolismo , Factores de Crecimiento Endotelial/metabolismo , Células 3T3 , Adulto , Anciano , Anciano de 80 o más Años , Animales , Axila/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/mortalidad , Neoplasias de la Mama Masculina/patología , Proteínas de Unión al Calcio , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/secundario , Carcinoma Intraductal no Infiltrante/mortalidad , Carcinoma Intraductal no Infiltrante/secundario , Carcinoma Lobular/mortalidad , Carcinoma Lobular/secundario , Células Cultivadas , Supervivencia sin Enfermedad , Familia de Proteínas EGF , Factores de Crecimiento Endotelial/genética , Femenino , Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Estimación de Kaplan-Meier , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Ratones , Persona de Mediana Edad , Invasividad Neoplásica , Especificidad de ÓrganosRESUMEN
BACKGROUND: Melanoma has the highest rate of spread to the leptomeninges and the incidence of melanoma has been steadily rising. This article describes recent experience at the Lille University Hospital, between 2007 and 2011 and discusses the possibilities for treatment of leptomeningeal metastasis. PATIENTS AND METHODS: Nine patients were diagnosed with leptomeningeal metastasis of melanoma. The standard criteria were used for the diagnosis. The treatment consisted of a combination of intrathecal chemotherapy, systemic chemotherapy and best supportive care. RESULTS: The overall median survival from the time of leptomeningeal metastasis diagnosis was eight weeks (range=1-168 weeks). In two cases, the median overall survival was 104 weeks. For these patients, there was a clear benefit in intrathecal chemotherapy combined with systemic treatment. No complication was observed. CONCLUSION: Despite a poor prognosis, treatment of melanoma leptomeningeal metastasis is needed in order to improve the quality of life, neurological progression-free survival and overall survival of patients.
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Antimetabolitos Antineoplásicos/administración & dosificación , Citarabina/administración & dosificación , Melanoma , Neoplasias Meníngeas , Supervivencia sin Enfermedad , Femenino , Humanos , Liposomas/administración & dosificación , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/secundario , Estadificación de Neoplasias , Pronóstico , Calidad de Vida , Tiotepa/administración & dosificaciónRESUMEN
Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-γ, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-γ. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control.
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Células Endoteliales/inmunología , Factores de Crecimiento Endotelial/inmunología , Proteínas/inmunología , Escape del Tumor/inmunología , Animales , Proteínas de Unión al Calcio , Adhesión Celular/genética , Adhesión Celular/inmunología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/inmunología , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Células Cultivadas , Progresión de la Enfermedad , Familia de Proteínas EGF , Células Endoteliales/patología , Factores de Crecimiento Endotelial/genética , Endotelio Vascular/inmunología , Endotelio Vascular/patología , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-12/metabolismo , Células Jurkat , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones SCID , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Proteínas/genética , Escape del Tumor/genética , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/inmunologíaRESUMEN
Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.
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Neoplasias Encefálicas/terapia , Germinoma/terapia , Recurrencia Local de Neoplasia/terapia , Neoplasias de Células Germinales y Embrionarias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/patología , Carboplatino/administración & dosificación , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Germinoma/patología , Humanos , Ifosfamida/administración & dosificación , Masculino , Recurrencia Local de Neoplasia/patología , Neoplasias de Células Germinales y Embrionarias/patología , Estudios Prospectivos , Dosificación Radioterapéutica , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE The indications of adjuvant chemotherapy for patients with estrogen receptor (ER) -positive breast cancer are controversial. We analyzed the predictive value of Ki67, HER2, and progesterone receptor (PR) expression for the efficacy of docetaxel in patients with ER-positive, node-positive breast cancer. PATIENTS AND METHODS Expression of Ki67, HER2, and PR was measured by immunohistochemistry in tumor samples from 798 patients with ER-positive breast cancer who participated in PACS01, a randomized trial that evaluated the efficacy of docetaxel. Risk reduction was evaluated using a Cox model adjusted for age, tumor size, nodal involvement, treatment arm, and biomarkers. The predictive value of biomarkers was assessed by an interaction test. Disease-free survival (DFS) was the primary end point. Results Ki67, HER2, and PR were expressed in 21%, 9%, and 62% of samples, respectively. Hazard ratios for relapse associated with docetaxel were 0.51 (95% CI, 0.26 to 1.01) in ER-positive/Ki67-positive tumors and 1.03 (95% CI, 0.69 to 1.55) in ER-positive/Ki67-negative tumors (ratio for interaction: 0.53; 95% CI, 0.24 to 1.16; P = .11). Five-year DFS rates were 81% (95% CI, 76% to 86%) and 84% (95% CI, 75% to 93%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with docetaxel and 81% (95% CI, 76% to 86%) and 62% (95% CI, 52% to 72%) in patients with ER-positive/Ki67-negative and ER-positive/Ki67-positive tumors treated with fluorouracil, epirubicin, and cisplatin. No trend for interaction was observed between docetaxel and HER2 (ratio for interaction: 0.83; 95% CI, 0.35 to 1.94; P = .66), nor between docetaxel and PR (ratio for interaction: 0.89; 95% CI, 0.47 to 1.66; P = .71). CONCLUSION Ki67 expression identifies a subset of patients with ER-positive breast cancer who could be sensitive to docetaxel treatment in the adjuvant setting.
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Neoplasias de la Mama/tratamiento farmacológico , Antígeno Ki-67/metabolismo , Taxoides/uso terapéutico , Adulto , Anciano , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Supervivencia sin Enfermedad , Docetaxel , Epirrubicina/uso terapéutico , Femenino , Humanos , Antígeno Ki-67/genética , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Receptores de Estrógenos/metabolismo , Resultado del TratamientoRESUMEN
OBJECTIVE: Cervical carcinomas mainly spread via lymphatics, stepwise from pelvic to aortic and scalenic lymph nodes. Metastatic nodes are the major prognostic factor in this disease. When scalenic nodes are involved, cervical cancer is considered to be disseminated. Since there is a major discrepancy in reported percentages of metastatic scalene nodes in the literature (0 to 50%), we proceeded to systematic pretreatment scalene node biopsy and then evaluated the validity of this procedure. METHODS: From January 1998 to May 2003, 72 patients with locally advanced cervical carcinoma and no suspicious paraaortic or scalenic nodes (respectively on magnetic resonance imaging and clinically) had a systematic surgical pretreatment lymph node evaluation (retroperitoneal laparoscopic infrarenal paraaortic lymph node dissection and left scalenic lymph node biopsy). Scalene biopsy was examined using hematoxylin/eosin stain and immunohistochemistry (KL1 antibodies). RESULTS: Among the 72 patients, 20 were stage IB2, 4 were IIA, 14 were IIB, 4 were IIIA, 27 were IIIB, 1 was IVA and 2 had a recurrent cervical carcinoma. Fourteen women had histologically confirmed paraaortic metastases (11 macroscopic, 3 microscopic). No metastatic involvement of the scalene nodes was detected. Fifteen patients developed a recurrence within 12 months (3 to 19 months). None of the patients developed scalenic recurrence. CONCLUSION: Left scalene node biopsy does not appear to be mandatory in routine pretherapeutic lymph node evaluation of patients with advanced cervical carcinoma and no clinical suspicious nodes. It may be useful to prove disseminated disease in patients with suspicious clinical nodes or hot spots on PET-scan, if fine needle biopsy is unconclusive.
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Escisión del Ganglio Linfático/métodos , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/patología , Adulto , Anciano , Aorta Abdominal/patología , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Persona de Mediana Edad , Cuello/patología , Estadificación de Neoplasias , Reproducibilidad de los ResultadosRESUMEN
Between February 2001 and March 2003, 542 sentinel lymph node procedures were performed for localised breast carcinoma (T0-T1, N0, M0) without any previous treatment. Frozen sections were performed in 515 cases and they did not reveal metastases in 446 cases. Fifty-two micrometastases < 2 mm and 18 macrometastases were reported by definitive histopathological exam. Axillary clearance was performed in 50/70 patients (38 with micrometastases and 12 for macrometastases). Modalities of histopathological procedure are discussed and particularly number and interval of serial slides with or without immunochemistry ; 81.8% (36/44) of micrometastases were detected on the two first serial sections. Decisional value of axillary clearance performed in case of micrometastases is also evaluated.