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1.
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
2.
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
3.
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
4.
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
6.
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
7.
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
8.
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
10.
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
11.
Radiology ; 295(2): 296-303, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32181727

RESUMO

Background The role of preoperative MRI for predicting surgical outcomes in patients diagnosed with ductal carcinoma in situ (DCIS) remains uncertain. Purpose To investigate the associations between preoperative MRI and surgical outcomes in DCIS confirmed by using US-guided core-needle biopsy (CNB) and to evaluate clinical-pathologic variables associated with a benefit from MRI. Materials and Methods Women with DCIS confirmed by using US-guided CNB between January 2012 and December 2016 were included in this retrospective study. Propensity score matching using 18 confounding covariates was used to create matched groups with MRI and without MRI, and surgical outcomes were compared. Clinical-pathologic variables were evaluated to determine women who benefited from MRI. Results A total of 541 women (mean age ± standard deviation, 50 years ± 10) were evaluated. Among 430 women who underwent MRI, 67 additional lesions (16%) were depicted, with 25 (37%) of the 67 additional lesions being malignant. Fifty-seven (13%) of the 430 women had a change in surgical plan because of their MRI findings; the change was appropriate for 31 (54%) women. In matched groups, the MRI group was associated with lower odds of positive resection margin (odds ratio [OR], 0.39; 95% confidence interval [CI]: 0.16, 0.93; P = .03) and repeat surgery (OR, 0.33; 95% CI: 0.12, 0.92; P = .03) compared with the non-MRI group. There was no difference in likelihood of initial mastectomy (OR, 1.2; 95% CI: 0.7, 2.0; P = .59) and overall mastectomy (OR, 0.93; 95% CI: 0.5, 1.6; P = .79). In the MRI group, low nuclear grade (90% [28 of 31] vs 69% [275 of 399]; P = .01), progesterone receptor positivity (81% [25 of 31] vs 61% [244 of 399]; P = .03), and human epidermal growth factor receptor 2 negativity (90% [28 of 31] vs 68% [270 of 399]; P = .01) were associated with a benefit from MRI versus no MRI. Conclusion Preoperative MRI depicted additional malignancy and reduced positive surgical margins and repeat surgery for ductal carcinoma in situ confirmed at US-guided biopsy without a higher mastectomy rate. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pinker in this issue.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma in Situ/diagnóstico por imagem , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/cirurgia , Imagem por Ressonância Magnética/métodos , Adulto , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Biópsia Guiada por Imagem , Margens de Excisão , Mastectomia , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Ultrassonografia de Intervenção , Ultrassonografia Mamária
12.
Clin Nucl Med ; 45(5): e232-e235, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32209879

RESUMO

Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Receptores de Somatostatina/metabolismo , Idoso , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Metástase Linfática , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Octreotida/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(11): e19506, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176095

RESUMO

RATIONALE: Accessory breast cancer is extremely rare among all cancerous diseases, especially in male patients. There were only few male axillary accessory breast cancer cases that have been reported in scientific literatures so far. Hereby, we would like to discuss a case of male axillary accessory breast cancer found in our hospital. PATIENT CONCERNS: We report a male senile patient suffering from a painful, enlarged, and hardened right axillary mass for more than 20 years. He came for further treatments due to progressive growth of the mass for 11 months with bloody ulceration for more than 1 month. DIAGNOSIS: Pathological examination manifested a grade II infiltrating ductal carcinoma derived from the accessory mammary gland (right axilla), with invasion of local skin. Immunohistochemical examination result: estrogen receptor (++) 90%, progesterone receptor (+++) 100%, human epidermal growth factor receptor-2 (1+), ki67 (20% positive), prostate specific antigen (-), caudal-related homeobox-2 (-), thyroid transcription factor-1 (-), Synaptophysin (+), NapsinA (1), and CK7 (-). INTERVENTIONS: Modified radical mastectomy and axillary lymph nodes clearance were performed on the accessary breast cancer under general anesthesia. Postoperatively, endocrine therapy was provided for the patient, orally-taken Letrozole was recommended for the rest of the patient's life. OUTCOMES: The patient recovered uneventfully and was discharged 3 days after the operation. The patient continued to take Letrozole orally regularly at home and no signs of recurrence were observed. CONCLUSION: Axillary accessory breast cancer in males is extremely rare, with no conspicuous and typical clinical presentations, which leads to inevitable neglect by clinicians. Therefore, there is significant necessity for clinicians to be cautious with this type of disease.


Assuntos
Doença de Alzheimer , Axila , Neoplasias da Mama Masculina/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Metástase Linfática/diagnóstico , Idoso de 80 Anos ou mais , Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Diagnóstico Diferencial , Humanos , Metástase Linfática/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Mastectomia Radical Modificada
14.
Chem Biol Interact ; 323: 109057, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32198086

RESUMO

Runx2 (Runt-related transcription factor 2) is a key transcription factor which is associated with osteoblast differentiation and expressed in ER+ (estrogen receptor positive) human breast cancer cell lines. Runx2 also participates in mammary gland development. Deregulation of RNA Pol III genes (polymerase III-dependent genes) is tightly linked to tumor development, while Brf1 (TFIIB-related factor 1) specifically regulates these gene transcription. However, nothing is known about the effect of Runx2 on Brf1 expression and Pol III gene transcription. Expression of Runx2, Brf1 and Pol III genes from the samples of human breast cancer and cell culture model were determined by the assays of RT-qPCR, immunoblot, luciferase reporter activity, immunohistochemistry, chromatin immunoprecipitation and Immunofluorescence. High expression of Runx2 is observed in the cases of breast cancer. The patients of high Runx2 expression at early stages display longer survival period, whereas the cases of high Runx2 at advanced stages reveal faster recurrence. The identification of signaling pathway indicates that JNK1 and c-Jun mediate Runx2 transcription. Repression of Runx2 reduces Brf1 expression and Pol III gene transcription. Further analysis indicates that Runx2 is colocalized with Brf1 in nucleus of breast cancer tissue. Both Runx2 and Brf1 synergistically modulate Pol III gene transcription. These studies indicate that Brf1 overexpression is able to be used as an early diagnosis biomarker of breast cancer, while high Runx2 expression indicates long survival period and faster recurrence. Runx2 mediates the deregulation of Brf1 and Pol III genes and its abnormal expression predicts the worse prognosis of breast cancer.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Etanol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , RNA Polimerase III/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Transcrição Genética/efeitos dos fármacos , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Transdução de Sinais , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/genética , Adulto Jovem
16.
Cancer Immunol Immunother ; 69(7): 1315-1326, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32198536

RESUMO

In view of the relatively limited efficacy of immunotherapies targeting the PD-1-PD-L1 axis in triple-negative breast cancer (TNBC) and of published reports on tumor-promoting roles of TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs), we determined the incidence of TNFR2+ TILs in TNBC patient tumors, their association with disease outcome and relations with PD-1+ TILs. Using a cohort of treatment-naïve TNBC patients with long follow-up (n = 70), we determined the presence of TNFR2+ TILs and PD-1+ TILs by immunohistochemistry. TILs (≥ 1% of cellular mass) and TNFR2+ TILs (≥ 1% of total TILs) were detected in 96% and 74% of tumors, respectively. The presence of TILs at > 5% of tumor cell mass ("Positive TILs"), as well as of positive TNFR2+ TILs (> 5%), was independently associated with good prognosis, and combination of both parameters demonstrated superior outcome relative to their lower levels. PD1+ TILs (> 5/hot spot) were detected in 63% of patients. High levels of PD-1+ TILs (> 20/hot spot) showed an unfavorable disease outcome, and in their presence, the favorable outcome of positive TNFR2+ TILs was ablated. Thus, TNFR2+ TILs are strongly connected to improved prognosis in TNBC; these findings suggest that TNFR2+ TILs have favorable effects in TNBC patients, unlike the tumor-promoting roles attributed to them in other cancer systems. Overall, our observations propose that the TNFR2+ TIL subset should not be targeted in the course of TNBC therapy; rather, its beneficial impacts may become into power when anti-PD-1 regimens-that may potentiate immune activities-are administered to TNBC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal de Mama/mortalidade , Linfócitos do Interstício Tumoral/imunologia , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
18.
Isr Med Assoc J ; 22(3): 160-163, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32147980

RESUMO

BACKGROUND: Male breast cancer (MBC) is a rare disease that is poorly understood. Treatment protocols are widely extrapolated from breast cancer in women. OBJECTIVES: To review the experience with MBC of a single center in Israel over a period of 22 years. METHODS: This single center retrospective study evaluated all patients diagnosed with MBC over a period of 22 years (1993-2015). Data were extracted from patient medical charts and included demographics, clinical, surgical, and oncological outcomes. RESULTS: The study comprised 49 patients. Mean age at diagnosis was 64.1 ± 13.5 years. The majority were diagnosed at early stages (1A-2A) (54.4%), 30.6% were stage 3B mostly due to direct skin and nipple involvement, and 59.2% of the patients had node negative disease. All of the patients were diagnosed with invasive ductal carcinoma and 30.6% had concomitant ductal carcinoma in situ. Estrogen receptor (ER) status was predominantly positive and luminal B (HER2-) was the most common subtype. Of the patients, 18.4% were BRCA carriers. The majority of patients underwent mastectomy. Radiotherapy was delivered to 46.9% and hormonal therapy to 89.8%. Chemotherapy was administered to 42.9%. Overall survival was 79.6% with a median survival of 60.1 (2-178) months; 5- and 10-year survival was 93.9% and 79.6%, respectively. Progesterone receptor (PR)-negative patients had a significantly improved overall survival. CONCLUSIONS: MBC has increasing incidence. PR-negative status was associated with better overall survival and disease-free interval. Indications to radiotherapy and hormonal therapy need standardization and will benefit from prospective randomized control trials.


Assuntos
Neoplasias da Mama Masculina/epidemiologia , Neoplasias da Mama Masculina/terapia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/terapia , Intervalo Livre de Doença , Humanos , Israel/epidemiologia , Masculino , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
Am Surg ; 86(2): 90-94, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167041

RESUMO

We aimed to evaluate the surgical margin outcomes and re-excision rates in patients undergoing bracketed seed localization of biopsy-proven breast cancer detected on screening mammogram. After approval by our Institutional Review Board, we retrospectively identified patients who had undergone iodine-125 seed localized lumpectomy at our institution from January 2010 to June 2017 by one of two fellowship-trained breast surgeons. Of those patients, a subset of 25 patients were identified who had undergone bracketed seed localization, defined as two or more seeds used to delineate the radiographic borders of the area of concern. All patients had originally presented with calcifications identified on screening mammogram that were subsequently diagnosed as ductal carcinoma in situ and/or invasive ductal carcinoma by image-guided biopsy performed at our institution. Eight patients had one positive margin on final surgical pathology and required re-excision (32%). One patient was converted to mastectomy. Of the patients requiring re-excision, the average maximum linear extent of calcifications was 3.4 cm (SD 0.97), whereas it was 3.1 cm (SD 1.2) in patients with negative surgical margins (P = 0.5). Bracketing calcifications with radioactive seeds can potentially allow more patients to undergo breast conservation surgery.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Radioisótopos do Iodo/administração & dosagem , Mastectomia Segmentar/métodos , Tratamentos com Preservação do Órgão/métodos , Neoplasias da Mama/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Feminino , Marcadores Fiduciais , Humanos , Biópsia Guiada por Imagem , Mamografia , Margens de Excisão , Reoperação/estatística & dados numéricos , Estudos Retrospectivos
20.
Cancer Radiother ; 24(2): 114-119, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32171675

RESUMO

PURPOSE: To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer. METHODS AND MATERIALS: Inclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20Gy/1 fraction): one dedicated electron linac (

Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Segunda Neoplasia Primária , Seleção de Pacientes , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Satisfação do Paciente , Intervalo Livre de Progressão , Estudos Prospectivos
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