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1.
J Exp Clin Cancer Res ; 39(1): 171, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32854728

RESUMO

The Covid-19 pandemic has challenged hard the national health systems worldwide. According to the national policy issued in March 2020 in response to the evolving Covid-19 pandemic, several hospitals were re-configured as Covid-19 centers and elective surgery procedures were rescheduled according to the most recent recommendations. In addition, Covid-19 protected cancer hubs were established, including the Regina Elena National Cancer Institute of Rome, Central Italy. At our Institute, the Breast Surgery Department continued working under the sign of a multidisciplinary approach. The number of professional figures involved in case evaluation was reduced to a minimum and interactions took place in the full respect of the required safety measures. Treatments for benign disease, pure prophylactic surgery and elective reconstructive procedures were all postponed and priority was assigned to the histologically-proven malignant breast tumors and highly suspicious lesions. From March 15th though April 30th 2020, we treated a total of 79 patients. This number is fully consistent with the average quantitative standards reached by our Department under ordinary circumstances. Patients were mostly discharged the day after surgery and none was readmitted due to surgery-related late complications. More generally, post-operative complications rates were unexpectedly low, particularly in light of the relatively high number of reconstructive procedures performed in this emergency situation. A strict follow up was performed based on the close contact with the surgical staff by telephone, messaging apps and telemedicine.Patients ascertainment for their Covid-19 status prior to hospital admission and hospital discharge allowed to maintain the "no-Covid-19" status at our Institution. In addition, during the aforementioned time window, none of the care providers developed SARS-CoV-2 infection or disease, as shown by the results of anti-SARS-CoV-2 immunoglobulin M and G profiling. In conclusions, elective breast cancer surgery procedures were successfully performed in a lockdown situation due to a novel viral pandemic. The well-coordinated regional and hospital efforts in terms of medical resource re-allocation and definition of clinical priorities allowed to maintain high quality standards of breast cancer care while ensuring safety to the cancer patients and care providers involved.


Assuntos
Betacoronavirus/isolamento & purificação , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Infecções por Coronavirus/prevenção & controle , Mastectomia/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Padrões de Prática Médica/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/virologia , Carcinoma Lobular/patologia , Carcinoma Lobular/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
2.
BMJ ; 370: m2836, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32816842

RESUMO

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. DESIGN: Prospective, open label, randomised controlled clinical trial. SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005). CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned. TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Idoso , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Cuidados Intraoperatórios , Mastectomia Segmentar , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida
3.
S Afr Med J ; 110(4): 296-301, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32657741

RESUMO

BACKGROUND: There has been no comprehensive study determining the financial burden of breast cancer in the South African (SA) public sector. OBJECTIVES: To develop a method to determine the cost of breast cancer treatment with chemotherapy per episode of care and to quantify the associated costs relating to chemotherapy at Groote Schuur Hospital (GSH), a government hospital in SA. These costs included costs associated with the management of adverse events arising from chemotherapy. METHODS: Retrospective patient-level data were collected for 200 patients from electronic databases and patient folders between 2013 and 2015. Direct medical costs were determined from the health funder's perspective. The information collected was categorised into the following cost components: chemotherapy medicines, support medicines, administration of chemotherapy, laboratory tests, radiology scans and imaging, doctor consultations and adverse events. Time-and-motion studies were conducted on a set of new patients and the data obtained were used for the study sample of 200 patients. All the above costs were used to determine the cost of chemotherapy per episode of care. The episode of care was defined as the care provided from 2 months prior to the date of commencing chemotherapy (pre-chemotherapy phase), during chemotherapy (treatment phase) and until 6 months after the date when the last cycle of chemotherapy was administered (follow-up phase). RESULTS: A method was developed to determine the episode-of-care costs for breast cancer at GSH. The total direct medical cost for treatment of breast cancer at GSH for 200 patients was ZAR3 154 877, and the average episode-of-care cost per patient was ZAR15 774. The average cost of management of adverse events arising from the various treatment modalities was ZAR13 133 per patient. It was found that the cost of treating a patient with adverse events was 1.8 times higher than the cost of treating a patient without adverse events. Of the patients, 86.5% managed to complete their prescribed chemotherapy treatment cycles, and the average cost of treatment of these patients was 1.3 times more than the average cost for patients who could not complete their treatment, based on the number of treatment cycles received. CONCLUSION: A comprehensive method to determine the costs associated with breast cancer management per episode of care was developed, and costs were quantified at GSH according to the treatment protocol used at the hospital.


Assuntos
Antineoplásicos/economia , Carcinoma de Mama in situ/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitais Públicos/economia , Adulto , Idoso , Carcinoma de Mama in situ/economia , Carcinoma de Mama in situ/patologia , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/economia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/economia , Carcinoma Lobular/patologia , Quimioterapia Adjuvante/economia , Técnicas de Laboratório Clínico/economia , Diagnóstico por Imagem/economia , Custos de Medicamentos/estatística & dados numéricos , Cuidado Periódico , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/economia , Cuidados Paliativos/economia , Honorários por Prescrição de Medicamentos/estatística & dados numéricos , Encaminhamento e Consulta/economia , Estudos Retrospectivos , África do Sul , Estudos de Tempo e Movimento , Adulto Jovem
4.
Medicine (Baltimore) ; 99(26): e20681, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590741

RESUMO

Plasma albumin to fibrinogen ratio is involved in human cancer, but its prognostic significance in breast cancer is controversy. In the context of breast invasive ductal carcinoma, this research aims to retrospectively evaluate by preoperative plasma albumin to fibrinogen ratio (AFR) and forecast oncological outcome and recurrence.This retrospective study comprised 230 patients with non-metastatic breast invasive ductal carcinoma who underwent surgery between January 2009 and April 2012 in Fourth Hospital of Hebei Medical University. Patients were categorized base on an optimal value of preoperative plasma fibrinogen (Fib) and albumin. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between albumin to fibrinogen ratio and clinical outcomes were assessed with univariate and multivariate analysis. A number of risk factors were used to form nomograms to evaluate survival, and Harrell concordance index (C-index) was used to evaluate the predictive accuracy.Plasma AFR was significantly associated with diminished disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed that plasma AFR was an independent prognostic indicator for DFS (HR = 1.346; 95% CI: 1.107-1.636; P = .03) and overall survival (OS) (HR = 1.485; 95% CI: 1.106-1.993; P = .008). Two prediction model of 3-, 5-years OS and DFS based on the AFR was developed.Elevated preoperative plasma AFR is an independent prognostic factor for oncological outcomes in patients with breast invasive ductal carcinoma. The formulated nomogram showed superior predictive accuracy for DFS and OS.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Fibrinogênio/análise , Nomogramas , Albumina Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
5.
Breast Cancer Res Treat ; 182(3): 679-688, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32562119

RESUMO

PURPOSE: As our hospitals conserve and re-allocate resources during the COVID-19 crisis, there is urgent need to determine how best to continue caring for breast cancer patients. During the time window before the COVID-19 critical peak and particularly thereafter, as hospitals are able to resume cancer operations, we anticipate that there will be great need to maximize efficiency to treat breast cancer. The goal of this study is to present a same-day protocol that minimizes resource utilization to enable hospitals to increase inpatient capacity, while providing care for breast cancer patients undergoing mastectomy and immediate breast reconstruction during the COVID-19 crisis. METHODS: IRB exempt patient quality improvement initiative was conducted to detail the operationalization of a novel same-day breast reconstruction protocol. Consecutive patients having undergone immediate breast reconstruction were prospectively enrolled between February and March of 2020 at Massachusetts General Hospital during the COVID-19 crisis. Peri-operative results and postoperative complications were summarized. RESULTS: Time interval from surgical closure to patient discharge was 5.02 ± 1.29 h. All patients were discharged home, with no re-admissions or emergency department visits. No postoperative complications were observed. CONCLUSION: This report provides an instruction manual to operationalize a same-day breast reconstruction protocol, to meet demands of providing appropriate cancer treatment during times of unprecedented resource limitations. Pre-pectoral implant-based breast reconstruction can be the definitive procedure or be used as a bridge to autologous reconstruction. Importantly, we hope this work will be helpful to our patients and community as we emerge from the COVID-19 pandemic.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Melhoria de Qualidade , Adulto , Assistência ao Convalescente , Anestesiologia , Betacoronavirus , Implante Mamário , Implantes de Mama , Protocolos Clínicos , Infecções por Coronavirus/epidemiologia , Eficiência , Serviço Hospitalar de Emergência , Feminino , Recursos em Saúde , Serviços de Assistência Domiciliar , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Pandemias , Readmissão do Paciente , Assistência Perioperatória/métodos , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Biópsia de Linfonodo Sentinela , Cirurgia Plástica , Oncologia Cirúrgica , Telemedicina , Dispositivos para Expansão de Tecidos
8.
Medicine (Baltimore) ; 99(25): e20809, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569228

RESUMO

RATIONALE: Pyrotinib is a novel dual pan-ErbB receptor tyrosine kinase inhibitor, approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, there was still limited information regarding specific effect of pyrotinib on HER2-positive MBC patients with phosphoinositol-3 kinase mutation. PATIENT CONCERNS: A 63-year-old woman accidentally discovered a left breast lesion. The breast cancer was diagnosed by biopsy of breast lesion and postoperative pathological examination in March, 2017. The patient was presented with HER2-positive (3+), invasive carcinoma of the left breast with lymph nodes and lung nodules metastasis, and the clinical stage was T4N2M1. However, the lesion continued to aggressive disease progression with the treatment of trastuzumab plus multiple chemotherapy regimens and traditional Chinese medicine. DIAGNOSES: The woman was diagnosed with invasive carcinoma of the left breast and lymph nodes and lung nodules metastasis. INTERVENTIONS: The patient received 6 cycles of pyrotinib in combination with capecitabine regularly. OUTCOMES: Progression free survival was more than 6 months, and the patient's efficacy evaluation was partial remission. LESSONS: Our clinical observations demonstrated that pyrotinib may be an effective treatment for patients with HER2-positive MBC.


Assuntos
Acrilamidas/uso terapêutico , Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Acrilamidas/administração & dosagem , Aminoquinolinas/administração & dosagem , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade
9.
PLoS One ; 15(6): e0234012, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544183

RESUMO

Understanding progression of breast cancers to invasive ductal carcinoma (IDC) can significantly improve breast cancer treatments. However, it is still difficult to identify genetic signatures and the role of tumor microenvironment to distinguish pathological stages of pre-invasive lesion and IDC. Presence of multiple subtypes of breast cancers makes the assessment more challenging. In this study, an in-vitro microfluidic assay was developed to quantitatively assess the subtype-specific invasion potential of breast cancers. The developed assay is a microfluidic platform in which a ductal structure of epithelial cancer cells is surrounded with a three-dimensional (3D) collagen matrix. In the developed platform, two triple negative cancer subtypes (MDA-MB-231 and SUM-159PT) invaded into the surrounding matrix but the luminal A subtype, MCF-7, did not. Among invasive subtypes, SUM-159PT cells showed significantly higher invasion and degradation of the surrounding matrix than MDA-MB-231. Interestingly, the cells cultured on the platform expressed higher levels of CD24 than in their conventional 2D cultures. This microfluidic platform may be a useful tool to characterize and predict invasive potential of breast cancer subtypes or patient-derived cells.


Assuntos
Carcinoma Ductal de Mama/patologia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral , Antígeno CD24/metabolismo , Carcinoma Ductal de Mama/classificação , Carcinoma Ductal de Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Microfluídica/métodos , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/genética
13.
Br J Radiol ; 93(1111): 20191019, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32401540

RESUMO

OBJECTIVE: To establish a radiomics nomogram by integrating clinical risk factors and radiomics features extracted from digital mammography (MG) images for pre-operative prediction of axillary lymph node (ALN) metastasis in breast cancer. METHODS: 216 patients with breast cancer lesions confirmed by surgical excision pathology were divided into the primary cohort (n = 144) and validation cohort (n = 72). Radiomics features were extracted from craniocaudal (CC) view of mammograms, and radiomics features selection were performed using the methods of ANOVA F-value and least absolute shrinkage and selection operator; then a radiomics signature was constructed with the method of support vector machine. Multivariate logistic regression analysis was used to establish a radiomics nomogram based on the combination of radiomics signature and clinical factors. The C-index and calibration curves were derived based on the regression analysis both in the primary and validation cohorts. RESULTS: 95 of 216 patients were confirmed with ALN metastasis by pathology, and 52 cases were diagnosed as ALN metastasis based on MG-reported criteria. The sensitivity, specificity, accuracy and AUC (area under the receiver operating characteristic curve of MG-reported criteria were 42.7%, 90.8%, 24.1% and 0.666 (95% confidence interval: 0.591-0.741]. The radiomics nomogram, comprising progesterone receptor status, molecular subtype and radiomics signature, showed good calibration and better favorite performance for the metastatic ALN detection (AUC 0.883 and 0.863 in the primary and validation cohorts) than each independent clinical features (AUC 0.707 and 0.657 in the primary and validation cohorts) and radiomics signature (AUC 0.876 and 0.862 in the primary and validation cohorts). CONCLUSION: The MG-based radiomics nomogram could be used as a non-invasive and reliable tool in predicting ALN metastasis and may facilitate to assist clinicians for pre-operative decision-making. ADVANCES IN KNOWLEDGE: ALN status remains among the most important breast cancer prognostic factors and is essential for making treatment decisions. However, the value of detecting metastatic ALN by MG is very limited. The studies on pre-operative ALN metastasis prediction using the method of MG-based radiomics in breast cancer are very few. Therefore, we studied whether MG-based radiomics nomogram could be used as a predictive biomarker for the detection of metastatic ALN.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Mamografia/métodos , Análise de Variância , Axila/diagnóstico por imagem , Axila/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Nomogramas , Estudos Retrospectivos
15.
Life Sci ; 253: 117722, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32348834

RESUMO

AIMS: It is well known that pyruvate dehydrogenase kinase 1 (PDK1) is highly expressed in breast cancer (BC) tissues and promotes tumor growth, but the underlying mechanisms of this process are unclear. Here, we investigated the effects of nuclear PDK1 on growth, migration and invasion in human BC cells. MAIN METHODS: The sub-cellular localization of PDK1 in BC cells was performed with subcellular fractionation followed by Western blot and immunofluorescence. The localization of PDK1 in breast normal tissue and breast duct carcinoma was detected by Immunohistochemistry. Then the protein-protein interaction between PDK1 and Importin ß was verified by co-immunoprecipitation assay. Finally, the effects of nuclear PDK1 on cell proliferation, apoptosis, migration and invasion of BC cells were assessed. KEY FINDINGS: In addition to its well-known sub-cellular localization, PDK1 was present in the nucleus of BC cells, and EGF treatment increased nucleus distribution of PDK1. Moreover, the level of nuclear PDK1 accumulation facilitated the growth of BC cells. We also found that the entry of PDK1 into nucleus mainly relied on the nuclear localization signal (NLS), and NLS mutation inhibited the entry of PDK1 into nucleus; as a result, the migration and invasion abilities of BC cells were impaired, and the number of apoptotic cells was significantly increased. SIGNIFICANCE: Our findings provided a new supplement to the sub-cellular localization of PDK1 in BC cells and uncovered the function of nuclear PDK1 in facilitating BC cells growth, migration and invasion.


Assuntos
Apoptose/fisiologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Quinase Piruvato Desidrogenase (Transferência de Acetil)/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Núcleo Celular/metabolismo , Proliferação de Células/fisiologia , Feminino , Humanos , Invasividade Neoplásica
16.
PLoS One ; 15(4): e0231004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271809

RESUMO

Blood and serum N-glycans can be used as markers for cancer diagnosis, as alterations in protein glycosylation are associated with cancer pathogenesis and progression. We aimed to develop a platform for breast cancer (BrC) diagnosis based on serum N-glycan profiles using MALDI-TOF mass spectroscopy. Serum N-glycans from BrC patients and healthy volunteers were evaluated using NosQuest's software "NosIDsys." BrC-associated "NosID" N-glycan biomarkers were selected based on abundance and NosIDsys analysis, and their diagnostic potential was determined using NosIDsys and receiver operating characteristic curves. Results showed an efficient pattern recognition of invasive ductal carcinoma patients, with very high diagnostic performance [area under the curve (AUC): 0.93 and 95% confidence interval (CI): 0.917-0.947]. We achieved effective stage-specific differentiation of BrC patients from healthy controls with 82.3% specificity, 84.1% sensitivity, and 82.8% accuracy for stage 1 BrC and recognized hormone receptor-2 and lymph node invasion subtypes based on N-glycan profiles. Our novel technique supplements conventional diagnostic strategies for BrC detection and can be developed as an independent platform for BrC screening.


Assuntos
Neoplasias da Mama/diagnóstico , Polissacarídeos/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/diagnóstico , Estudos de Casos e Controles , Feminino , Glicosilação , Humanos , Curva ROC , Sensibilidade e Especificidade
17.
Nat Commun ; 11(1): 1723, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265444

RESUMO

Metaplastic breast carcinoma (MBC) is a highly aggressive form of triple-negative cancer (TNBC), defined by the presence of metaplastic components of spindle, squamous, or sarcomatoid histology. The protein profiles underpinning the pathological subtypes and metastatic behavior of MBC are unknown. Using multiplex quantitative tandem mass tag-based proteomics we quantify 5798 proteins in MBC, TNBC, and normal breast from 27 patients. Comparing MBC and TNBC protein profiles we show MBC-specific increases related to epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways. MBC subtypes exhibit distinct upregulated profiles, including translation and ribosomal events in spindle, inflammation- and apical junction-related proteins in squamous, and extracellular matrix proteins in sarcomatoid subtypes. Comparison of the proteomes of human spindle MBC with mouse spindle (CCN6 knockout) MBC tumors reveals a shared spindle-specific signature of 17 upregulated proteins involved in translation and 19 downregulated proteins with roles in cell metabolism. These data identify potential subtype specific MBC biomarkers and therapeutic targets.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteoma/metabolismo , Sarcoma/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundário , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundário , Transição Epitelial-Mesenquimal/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Redes e Vias Metabólicas/genética , Metaplasia/genética , Metaplasia/metabolismo , Camundongos , Pessoa de Meia-Idade , Mutação , Biossíntese de Proteínas/genética , Proteoma/genética , Proteômica , Sarcoma/genética , Sarcoma/secundário , Fuso Acromático/genética , Fuso Acromático/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
18.
Cancer Immunol Immunother ; 69(8): 1437-1446, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32266446

RESUMO

V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint that is an emerging target for cancer immunotherapy. This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as well as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast [corrected]. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expressed in samples that were estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2-positive, poorly differentiated, human epidermal growth factor receptor 2-enriched, and consisting of basal-like tumors. VISTA on immune cells correlated with PD-1, PD-L1, stromal CD8, and tumor-infiltrating lymphocyte expression and was an independent prognostic factor for improved relapse-free and disease-specific survival in patients with estrogen receptor-negative, progesterone receptor-negative, and basal-like IDC. These findings support therapeutic strategies that modulate VISTA expression, perhaps in combination with PD-1/PD-L1 blockade, in human breast cancer immunotherapy.


Assuntos
Antígenos B7/metabolismo , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
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