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1.
Breast Cancer Res Treat ; 205(2): 267-279, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453781

RESUMO

PURPOSE: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status. METHODS: Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity. RESULTS: Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9-85.4) vs. 71.9% (95%CI: 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8-83.2) vs. 61.5% (95%CI: 42.5-77.6), 82.4% (95%CI: 62.2-93.6) vs. 100% (95%CI: 74.1-100), and 90% (95%CI: 69.8-98.3) vs. 100% (95%CI: 74.1-100). Toxicity profile was consistent with previous reports. CONCLUSION: Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned. TRIAL REGISTRATION NUMBER: NCT02339532 (registered on 14/12/14).


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Carboplatina , DNA Topoisomerases Tipo II , Docetaxel , Terapia Neoadjuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pessoa de Meia-Idade , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/genética , Receptor ErbB-2/metabolismo , Adulto , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/administração & dosagem , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Proteínas de Ligação a Poli-ADP-Ribose/genética , Antraciclinas/administração & dosagem , Antraciclinas/uso terapêutico , Epirubicina/administração & dosagem
2.
Ann Pathol ; 41(6): 507-520, 2021 Nov.
Artigo em Francês | MEDLINE | ID: mdl-34393014

RESUMO

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Receptor ErbB-2/genética
3.
BMC Cancer ; 18(1): 129, 2018 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-29394917

RESUMO

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Thus, it has been suggested that TIL density or/and immunophenotype could serve as biomarkers for selection of IBC patients for immunotherapy. However, much less is known about significance of TILs in breast ductal carcinoma in situ (DCIS). METHODS: We retrospectively investigated TIL density and immunophenotype in 96 pure DCIS and 35 microinvasive carcinomas (miCa). TIL density was assessed on H&E-stained breast biopsy sections as the percentage of tumour stromal area occupied by TILs, and classified into 4 grades: 0 (0%-9%), 1 (10-29%), 2 (30-49%) and 3 (50%-100%). TIL immunophenotype was assessed by immunohistochemistry for CD8, CD4, FoxP3, CD38 or CD20. RESULTS: Compared to pure DCIS, miCa contained significantly more cases with TIL density grade 3 (p = 0.028). Concordantly, CD8+, CD4+ and CD38+ cells were more numerous in miCa than in pure DCIS. In the pure DCIS subgroup with TIL density grades 2 and 3, all TIL subpopulations were more numerous than in the pure DCIS with TIL density grades 0 and 1, however the ratio between T-lymphocytes (CD8+ and CD4+) and B-lymphocytes (CD20+) was significantly lower (p = 0.029). On the other side, this ratio was significantly higher in miCa, in comparison with pure DCIS having TIL density grades 2 and 3 (p = 0.017). By cluster analysis of tumour cell pathobiological features we demonstrated similarity between miCa and the pure DCIS with TIL density grades 2 and 3. The only significant difference between those two categories was in the ratio of T- to B-TILs, higher in miCa. CONCLUSION: Results indicate that TIL density level can distinguish 2 biologically different DCIS subgroups, one of which (DCIS with ≥30% TILs, the TIL-rich DCIS) is like miCa. Similarity of TIL-rich pure DCIS and miCa as well as the role of B-lymphocytes in DCIS invasiveness are worth further investigating with regards to the potential development of immunotherapy-based prevention of DCIS progression.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Linfócitos do Interstício Tumoral/patologia , Adulto , Idoso , Neoplasias da Mama/imunologia , Carcinoma Intraductal não Infiltrante/imunologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Ann Pathol ; 36(1): 73-9, 2016 Jan.
Artigo em Francês | MEDLINE | ID: mdl-26778816

RESUMO

Nowadays, the analysis of theranostic molecular markers is central in the management of lung cancer. As those tumors are diagnosed in two third of the cases at an advanced stage, molecular screening is frequently performed on "small samples". The screening strategy starts by an accurate histopathological characterization, including on biopsies or cytological specimens. WHO 2015 provided a new classification for small biopsy and cytology, defining categories such as non-small cell carcinoma (NSCC), favor adenocarcinoma (TTF1 positive), or favor squamous cell carcinoma (p40 positive). Only the NSCC tumors, non-squamous, are eligible to molecular testing. A strategy aiming at tissue sparing for the small biopsies has to be organized. Tests corresponding to available drugs are prioritized. Blank slides will be prepared for immunohistochemistry and in situ hybridization based tests such as ALK. DNA will then be extracted for the other tests, EGFR mutation screening first associated or not to KRAS. Then, the emerging biomarkers (HER2, ROS1, RET, BRAF…) as well as potentially other markers in case of clinical trials, can been tested. The spread of next generation sequencing technologies, with a very sensitive all-in-one approach will allow the identification of minority clones. Eventually, the development of liquid biopsies will provide the opportunity to monitor the apparition of resistance clones during treatment. This non-invasive approach allows patients with a contraindication to perform biopsy or with non-relevant biopsies to access to molecular screening.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/diagnóstico , Técnicas de Diagnóstico Molecular , Proteínas de Neoplasias/análise , Algoritmos , Biomarcadores Tumorais/genética , Biópsia , Contraindicações , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica/métodos , Hibridização In Situ , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/genética , Translocação Genética
5.
Expert Rev Mol Diagn ; 23(12): 1283-1291, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37906110

RESUMO

BACKGROUND: ALK, ROS1 and RET rearrangements occur, respectively, in 5%, 2%, and 1% non-small cell lung cancers (NSCLC). ALK and ROS1 fusion proteins detection by immunohistochemistry (IHC) has been validated for rapid patient screening, but ROS1 fusions need to be confirmed by another technique and no RET IHC test is available for clinical use. RESEARCH DESIGN AND METHODS: We report herein the usefulness of the HTG EdgeSeq Assay, an RNA extraction-free test combining a quantitative nuclease protection assay with NGS, for the detection of ALK, ROS1 and RET fusions from 'real-life' small NSCLC samples. A total of 203 FFPE samples were collected from 11 centers. They included 143 rearranged NSCLC (87 ALK, 39 ROS1, 17 RET) and 60 ALK-ROS1-RET negative controls. RESULTS: The assay had a specificity of 98% and a sensitivity for ALK, ROS1 and RET fusions of 80%, 94% and 100% respectively. Among the 19 HTG-assay false negative samples, the preanalytical conditions were identified as the major factors impacting the assay efficiency. CONCLUSIONS: Overall, the HTG EdgeSeq assay offers comparable sensitivities and specificity than other RNA sequencing techniques, with the advantage that it can be used on very small and old samples collected multicentrically.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inclusão em Parafina , Humanos , Quinase do Linfoma Anaplásico/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Proteínas de Fusão Oncogênica/análise , Proteínas Tirosina Quinases/análise , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-ret/análise , Proteínas Proto-Oncogênicas c-ret/metabolismo , RNA , Imunoquímica/métodos
6.
PLoS One ; 11(2): e0148739, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26859833

RESUMO

BACKGROUND: Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. METHODS: This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. RESULTS: Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis, OCT3 remains an independent criterion for adjuvant FOLFOX chemotherapy response (p = 0.039). No significant relation is reported between chemotherapy response and the expression of OCT1 (p = 0.49), OCT2 (p = 0.09), CTR1 (p = 0.45), ATP7B (p = 0.94) and Ki-67 (p = 0.34) in tumors. CONCLUSIONS: High expression of OCT3 could be an independent factor related to resistance to FOLFOX-4 chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Transporte de Cátions/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Compostos Organoplatínicos/metabolismo , Adenosina Trifosfatases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimioterapia Adjuvante , Transportador de Cobre 1 , ATPases Transportadoras de Cobre , Feminino , Fluoruracila/uso terapêutico , Humanos , Imuno-Histoquímica , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 1 de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Estudos Retrospectivos , Resultado do Tratamento
7.
World J Gastrointest Surg ; 6(3): 42-6, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24672649

RESUMO

Mucinous cystic adenoma (MCA) of the pancreas is a rare benign cystic tumor with ovarian-like stroma and lack of communication with the pancreatic ductal system. The ovarian tissue is incorporated from the left gonad within the dorsal pancreas during embryogenesis. Consequently, congenital dorsal agenesis of the pancreas (DAP) cannot be associated with MCA. We report the case of a giant MCA associated with atrophy of the dorsal pancreas mimicking complete DAP. Pancreato-magnetic resonance imaging failed to identify the dorsal pancreas but the absence of diabetes mellitus and compression of the splenic vein with major tributaries rectified the diagnosis of secondary atrophy of the distal pancreas. Unusual proximal location of the cyst in the pancreas may have induced chronic obstruction of both the dorsal pancreatic duct and the splenic vein, with secondary atrophy of the distal pancreas.

8.
World J Gastroenterol ; 19(18): 2826-9, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23687421

RESUMO

Right portal vein ligation (PVL) is a safe and widespread procedure to induce controlateral liver hypertrophy for the treatment of bilobar colorectal liver metastases. We report a case of a 60-year-old man treated by both right PVL and ligation of the glissonian branches of segment 4 for colorectal liver metastases surrounding the right and median hepatic veins. After surgery, the patient developed massive hepatic necrosis with secondary pulmonary and renal insufficiency requiring transfer to the intensive care unit. This so-called toxic liver syndrome finally regressed after hemofiltration and positive oxygen therapy. Diagnosis of acute congestion of the ligated lobe was suspected. The mechanism suspected was an increase in arterial inflow secondary to portal vein ligation concomitant with a decrease in venous outflow due to liver metastases encircling the right and median hepatic vein. This is the first documented case of toxic liver syndrome in a non-cirrhotic patient with favorable issue, and a rare complication of PVL.


Assuntos
Neoplasias Colorretais/patologia , Hepatopatias/etiologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Biópsia , Hemofiltração , Humanos , Ligadura , Hepatopatias/patologia , Hepatopatias/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Necrose , Oxigenoterapia , Veia Porta/diagnóstico por imagem , Insuficiência Renal/etiologia , Insuficiência Respiratória/etiologia , Síndrome , Resultado do Tratamento
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