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  1 / 20520 MEDLINE  
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[PMID]:29318276
[Au] Autor:Plevritis SK; Munoz D; Kurian AW; Stout NK; Alagoz O; Near AM; Lee SJ; van den Broek JJ; Huang X; Schechter CB; Sprague BL; Song J; de Koning HJ; Trentham-Dietz A; van Ravesteyn NT; Gangnon R; Chandler Y; Li Y; Xu C; Ergun MA; Huang H; Berry DA; Mandelblatt JS
[Ad] Endereço:Departments of Radiology and Biomedical Data Science, School of Medicine, Stanford University, Stanford, California.
[Ti] Título:Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012.
[So] Source:JAMA;319(2):154-164, 2018 01 09.
[Is] ISSN:1538-3598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Given recent advances in screening mammography and adjuvant therapy (treatment), quantifying their separate and combined effects on US breast cancer mortality reductions by molecular subtype could guide future decisions to reduce disease burden. Objective: To evaluate the contributions associated with screening and treatment to breast cancer mortality reductions by molecular subtype based on estrogen-receptor (ER) and human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu). Design, Setting, and Participants: Six Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2012 using national data on plain-film and digital mammography patterns and performance, dissemination and efficacy of ER/ERBB2-specific treatment, and competing mortality. Multiple US birth cohorts were simulated. Exposures: Screening mammography and treatment. Main Outcomes and Measures: The models compared age-adjusted, overall, and ER/ERBB2-specific breast cancer mortality rates from 2000 to 2012 for women aged 30 to 79 years relative to the estimated mortality rate in the absence of screening and treatment (baseline rate); mortality reductions were apportioned to screening and treatment. Results: In 2000, the estimated reduction in overall breast cancer mortality rate was 37% (model range, 27%-42%) relative to the estimated baseline rate in 2000 of 64 deaths (model range, 56-73) per 100 000 women: 44% (model range, 35%-60%) of this reduction was associated with screening and 56% (model range, 40%-65%) with treatment. In 2012, the estimated reduction in overall breast cancer mortality rate was 49% (model range, 39%-58%) relative to the estimated baseline rate in 2012 of 63 deaths (model range, 54-73) per 100 000 women: 37% (model range, 26%-51%) of this reduction was associated with screening and 63% (model range, 49%-74%) with treatment. Of the 63% associated with treatment, 31% (model range, 22%-37%) was associated with chemotherapy, 27% (model range, 18%-36%) with hormone therapy, and 4% (model range, 1%-6%) with trastuzumab. The estimated relative contributions associated with screening vs treatment varied by molecular subtype: for ER+/ERBB2-, 36% (model range, 24%-50%) vs 64% (model range, 50%-76%); for ER+/ERBB2+, 31% (model range, 23%-41%) vs 69% (model range, 59%-77%); for ER-/ERBB2+, 40% (model range, 34%-47%) vs 60% (model range, 53%-66%); and for ER-/ERBB2-, 48% (model range, 38%-57%) vs 52% (model range, 44%-62%). Conclusions and Relevance: In this simulation modeling study that projected trends in breast cancer mortality rates among US women, decreases in overall breast cancer mortality from 2000 to 2012 were associated with advances in screening and in adjuvant therapy, although the associations varied by breast cancer molecular subtype.
[Mh] Termos MeSH primário: Neoplasias da Mama/mortalidade
Detecção Precoce de Câncer
Mamografia
Modelos Estatísticos
[Mh] Termos MeSH secundário: Neoplasias da Mama/diagnóstico por imagem
Neoplasias da Mama/terapia
Feminino
Seres Humanos
Mamografia/métodos
Mortalidade/tendências
Receptor ErbB-2
Receptores Estrogênicos
Estados Unidos/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Receptors, Estrogen); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1001/jama.2017.19130


  2 / 20520 MEDLINE  
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[PMID]:29381731
[Au] Autor:Luo H; Xu X; Ye M; Sheng B; Zhu X
[Ad] Endereço:Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
[Ti] Título:The prognostic value of HER2 in ovarian cancer: A meta-analysis of observational studies.
[So] Source:PLoS One;13(1):e0191972, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The prognostic role of human epidermal growth factor receptor 2 (HER2) in ovarian cancer has been investigated in previous studies, but the results remain controversial. Here we present a meta-analysis to systematically review the association between HER2 expression and ovarian cancer prognosis. METHOD: Observational studies published until July 2017 were searched in Pubmed, Embase, and Cochrane library databases. Hazard ratios (HRs) for survival with 95% confidence intervals (CIs), subgroup analyses, publication bias and sensitivity analyses were implemented under a standard manner. Estimates of overall survival (OS), progress-free survival (PFS) and disease-free survival (DFS) were weighted and pooled using Der Simonian-Laird random-effect model. RESULT: Thirty-four studies that include 5180 ovarian cancer patients were collected for analysis. Expression of HER2 was negatively correlated with clinical prognosis of overall survival (HR = 1.57, 95% CI: 1.31 to 1.89, P < 0.001) and disease-free survival / progress-free survival (HR = 1.26, 95% CI = 1.06 to 1.49) in ovarian cancers. The association between HER2 expression and poor ovarian cancer prognosis in overall survival was also statistically significant in subgroups of unclassified ovarian cancer, Caucasian population and Asian population, while irrespective of detection method. CONCLUSION: HER2 expression was related with poor prognosis in ovarian cancer patients and can be used as a predicting cancer prognostic biomarker in ovarian cancer patients.
[Mh] Termos MeSH primário: Neoplasias Ovarianas/patologia
Receptor ErbB-2/metabolismo
[Mh] Termos MeSH secundário: Intervalo Livre de Doença
Feminino
Seres Humanos
Estudos Observacionais como Assunto
Neoplasias Ovarianas/metabolismo
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191972


  3 / 20520 MEDLINE  
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[PMID]:28456837
[Au] Autor:Ulaner GA; Castillo R; Wills J; Gönen M; Goldman DA
[Ad] Endereço:Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ulanerg@mskcc.org.
[Ti] Título:F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer.
[So] Source:Eur J Nucl Med Mol Imaging;44(9):1420-1427, 2017 Aug.
[Is] ISSN:1619-7089
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: This study assesses F-FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer. METHODS: In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent F-FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery. F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI). RESULTS: A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, F-FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, F-FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9-20%). CONCLUSIONS: F-FDG-PET/CT revealed distant metastases in 14% (95% CI: 9-20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9-24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with F-FDG-PET/CT at the time of initial diagnosis.
[Mh] Termos MeSH primário: Neoplasias da Mama/diagnóstico por imagem
Neoplasias da Mama/patologia
Fluordesoxiglucose F18
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
Receptor ErbB-2/metabolismo
Receptores Estrogênicos/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Neoplasias da Mama/metabolismo
Feminino
Seres Humanos
Meia-Idade
Estadiamento de Neoplasias
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Estrogen); 0Z5B2CJX4D (Fluorodeoxyglucose F18); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE
[do] DOI:10.1007/s00259-017-3709-1


  4 / 20520 MEDLINE  
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[PMID]:29489698
[Au] Autor:Zuradelli M; Masci G; Ferraro E; Losurdo A; De Sanctis R; Torrisi R; Santoro A
[Ti] Título:Never too old to fight breast cancer: A case report.
[So] Source:Medicine (Baltimore);97(9):e9981, 2018 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Breast cancer is the most common cancer affecting females worldwide and its lifetime risk increases with age. Human epidermal growth factor receptor gene-2 (HER-2) positive breast cancer represents about 20% of all breast cancers, 1 out of 10 is diagnosed in women over 70 years of age. It tends to be more aggressive and to spread more quickly than other subtypes, but the introduction in clinical practice of new anti-HER-2 agents combined with chemotherapy has significantly improved progression free and overall survival. Elderly patients are frequently undertreated because of concerns about their age, performance status, and comorbidities. Here, we report a case of an octogenarian patient treated with T-DM1 with brilliant results. PATIENT CONCERNS: An 87 years old woman affected with HER-2 positive breast cancer presented progression of disease with lymph node and skin metastases after 3 lines of chemoimmunotherapy. DIAGNOSES: Breast cancer in elderly patient, lymph node, and skin metastases. INTERVENTIONS: Chemoimmunotherapy (trastuzumab emtansine). OUTCOME: Objective response of the disease and significant clinical benefit. LESSONS: This case clearly suggests that age and comorbidities do not always represent an absolute contraindication to combined treatments.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Maitansina/análogos & derivados
Trastuzumab/uso terapêutico
[Mh] Termos MeSH secundário: Idoso de 80 Anos ou mais
Neoplasias da Mama/química
Neoplasias da Mama/patologia
Feminino
Seres Humanos
Linfonodos/patologia
Metástase Linfática
Maitansina/uso terapêutico
Receptor ErbB-2/análise
Neoplasias Cutâneas/tratamento farmacológico
Neoplasias Cutâneas/secundário
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 14083FR882 (Maytansine); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); P188ANX8CK (Trastuzumab); SE2KH7T06F (ado-trastuzumab emtansine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009981


  5 / 20520 MEDLINE  
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[PMID]:29028222
[Au] Autor:Choi HJ; Joo HS; Won HY; Min KW; Kim HY; Son T; Oh YH; Lee JY; Kong G
[Ad] Endereço:Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea; Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University,
[Ti] Título:Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer.
[So] Source:J Natl Cancer Inst;110(4), 2018 Apr 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Despite the benefit of endocrine therapy, acquired resistance during or after treatment still remains a major challenge in estrogen receptor (ER)-positive breast cancer. We investigated the potential role of histone demethylase retinoblastoma-binding protein 2 (RBP2) in endocrine therapy resistance of breast cancer. Methods: Survival of breast cancer patients according to RBP2 expression was analyzed in three different breast cancer cohorts including METABRIC (n = 1980) and KM plotter (n = 1764). RBP2-mediated tamoxifen resistance was confirmed by invitro sulforhodamine B (SRB) colorimetric, colony-forming assays, and invivo xenograft models (n = 8 per group). RNA-seq analysis and receptor tyrosine kinase assay were performed to identify the tamoxifen resistance mechanism by RBP2. All statistical tests were two-sided. Results: RBP2 was associated with poor prognosis to tamoxifen therapy in ER-positive breast cancer (P = .04 in HYU cohort, P = .02 in KM plotter, P = .007 in METABRIC, log-rank test). Furthermore, RBP2 expression was elevated in patients with tamoxifen-resistant breast cancer (P = .04, chi-square test). Knockdown of RBP2 conferred tamoxifen sensitivity, whereas overexpression of RBP2 induced tamoxifen resistance invitro and invivo (MCF7 xenograft: tamoxifen-treated control, mean [SD] tumor volume = 70.8 [27.9] mm3, vs tamoxifen-treated RBP2, mean [SD] tumor volume = 387.9 [85.1] mm3, P < .001). Mechanistically, RBP2 cooperated with ER co-activators and corepressors and regulated several tamoxifen resistance-associated genes, including NRIP1, CCND1, and IGFBP4 and IGFBP5. Furthermore, epigenetic silencing of IGFBP4/5 by RBP2-ER-NRIP1-HDAC1 complex led to insulin-like growth factor-1 receptor (IGF1R) activation. RBP2 also increased IGF1R-ErbB crosstalk and subsequent PI3K-AKT activation via demethylase activity-independent ErbB protein stabilization. Combinational treatment with tamoxifen and PI3K inhibitor could overcome RBP2-mediated tamoxifen resistance (RBP2-overexpressing cells: % cell viability [SD], tamoxifen = 89.0 [3.8]%, vs tamoxifen with BKM120 = 41.3 [5.6]%, P < .001). Conclusions: RBP2 activates ER-IGF1R-ErbB signaling cascade in multiple ways to induce tamoxifen resistance, suggesting that RBP2 is a potential therapeutic target for ER-driven cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Carcinoma Ductal de Mama/metabolismo
Resistência a Medicamentos Antineoplásicos
Proteínas de Neoplasias/fisiologia
Receptores Estrogênicos/metabolismo
Proteína 2 de Ligação ao Retinoblastoma/fisiologia
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Análise de Variância
Animais
Antineoplásicos Hormonais/uso terapêutico
Neoplasias da Mama/química
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Carcinoma Ductal de Mama/química
Carcinoma Ductal de Mama/tratamento farmacológico
Carcinoma Ductal de Mama/patologia
Proteínas de Transporte/metabolismo
Estudos de Coortes
Colorimetria
Intervalo Livre de Doença
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Xenoenxertos
Seres Humanos
Estimativa de Kaplan-Meier
Células MCF-7
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Proteínas de Neoplasias/metabolismo
Células-Tronco Neoplásicas
Proteínas Nucleares/metabolismo
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/metabolismo
Receptor ErbB-2/metabolismo
Receptor IGF Tipo 1/metabolismo
Proteína 2 de Ligação ao Retinoblastoma/metabolismo
Tamoxifeno/uso terapêutico
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Antineoplastic Agents, Hormonal); 0 (Carrier Proteins); 0 (IGFBP5-interacting protein, human); 0 (Neoplasm Proteins); 0 (Nuclear Proteins); 0 (Receptors, Estrogen); 0 (nuclear receptor interacting protein 1); 094ZI81Y45 (Tamoxifen); EC 1.14.11.27 (Retinoblastoma-Binding Protein 2); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Receptor, ErbB-2); EC 2.7.10.1 (Receptor, IGF Type 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx207


  6 / 20520 MEDLINE  
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[PMID]:28859290
[Au] Autor:Troester MA; Sun X; Allott EH; Geradts J; Cohen SM; Tse CK; Kirk EL; Thorne LB; Mathews M; Li Y; Hu Z; Robinson WR; Hoadley KA; Olopade OI; Reeder-Hayes KE; Earp HS; Olshan AF; Carey LA; Perou CM
[Ad] Endereço:Department of Epidemiology, Lineberger Comprehensive Cancer Center; Department of Pathology and Lab Medicine, Department of Nutrition (EHA), and Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC; Dana Farber Cancer Institute, Harvard University, Boston, MA; Center
[Ti] Título:Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study.
[So] Source:J Natl Cancer Inst;110(2), 2018 Feb 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: African American breast cancer patients have lower frequency of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative disease and higher subtype-specific mortality. Racial differences in molecular subtype within clinically defined subgroups are not well understood. Methods: Using data and biospecimens from the population-based Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified 980 invasive breast cancers using RNA expression-based PAM50 subtype and recurrence (ROR) score that reflects proliferation and tumor size. Molecular subtypes (Luminal A, Luminal B, HER2-enriched, and Basal-like) and ROR scores (high vs low/medium) were compared by race (blacks vs whites) and age (≤50 years vs > 50 years) using chi-square tests and analysis of variance tests. Results: Black women of all ages had a statistically significantly lower frequency of Luminal A breast cancer (25.4% and 33.6% in blacks vs 42.8% and 52.1% in whites; younger and older, respectively). All other subtype frequencies were higher in black women (case-only odds ratio [OR] = 3.11, 95% confidence interval [CI] = 2.22 to 4.37, for Basal-like; OR = 1.45, 95% CI = 1.02 to 2.06, for Luminal B; OR = 2.04, 95% CI = 1.33 to 3.13, for HER2-enriched). Among clinically HR+/HER2- cases, Luminal A subtype was less common and ROR scores were statistically significantly higher among black women. Conclusions: Multigene assays highlight racial disparities in tumor subtype distribution that persist even in clinically defined subgroups. Differences in tumor biology (eg, HER2-enriched status) may be targetable to reduce disparities among clinically ER+/HER2- cases.
[Mh] Termos MeSH primário: Afroamericanos
Neoplasias da Mama/química
Neoplasias da Mama/etnologia
Grupo com Ancestrais do Continente Europeu
RNA Neoplásico/análise
Receptor ErbB-2/análise
Receptores Estrogênicos/análise
Receptores de Progesterona/análise
[Mh] Termos MeSH secundário: Adulto
Idoso
Neoplasias da Mama/genética
Neoplasias da Mama/patologia
Proliferação Celular
Feminino
Seres Humanos
Meia-Idade
Recidiva
Carga Tumoral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Neoplasm); 0 (Receptors, Estrogen); 0 (Receptors, Progesterone); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx135


  7 / 20520 MEDLINE  
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[PMID]:28453704
[Au] Autor:Lesurf R; Griffith OL; Griffith M; Hundal J; Trani L; Watson MA; Aft R; Ellis MJ; Ota D; Suman VJ; Meric-Bernstam F; Leitch AM; Boughey JC; Unzeitig G; Buzdar AU; Hunt KK; Mardis ER
[Ad] Endereço:McDonnell Genome Institute at Washington University School of Medicine, St Louis, USA
[Ti] Título:Genomic characterization of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy-results from the ACOSOG Z1041 (Alliance) trial.
[So] Source:Ann Oncol;28(5):1070-1077, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: HER2 (ERBB2) gene amplification and its corresponding overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents are effective treatments, resistance remains a major cause of death. The American College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to compare the pathologic complete response (pCR) rate of distinct regimens of neoadjuvant chemotherapy and trastuzumab, but ultimately identified no difference. Patients and methods: In supplement to tissues from 37 Z1041 cases, 11 similarly treated cases were obtained from a single institution study (NCT00353483). We have extracted genomic DNA from both pre-treatment tumor biopsies and blood of these 48 cases, and performed whole genome (WGS) and exome sequencing. Coincident with these efforts, we have generated RNA-seq profiles from 42 of the tumor biopsies. Among patients in this cohort, 24 (50%) achieved a pCR. Results: We have characterized the genomic landscape of HER2-positive breast cancer and investigated associations between genomic features and pCR. Cases assigned to the HER2-enriched subtype by RNA-seq analysis were more likely to achieve a pCR compared to the luminal, basal-like, or normal-like subtypes (19/27 versus 3/15; P = 0.0032). Mutational events led to the generation of putatively active neoantigens, but were overall not associated with pCR. ERBB2 and GRB7 were the genes most commonly observed in fusion events, and genomic copy number analysis of the ERBB2 locus indicated that cases with either no observable or low-level ERBB2 amplification were less likely to achieve a pCR (7/8 versus 17/40; P = 0.048). Moreover, among cases that achieved a pCR, tumors consistently expressed immune signatures that may contribute to therapeutic response. Conclusion: The identification of these features suggests that it may be possible to predict, at the time of diagnosis, those HER2-positive breast cancer patients who will not respond to treatment with chemotherapy and trastuzumab. ClinicalTrials.gov identifiers: NCT00513292, NCT00353483.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Trastuzumab/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Neoplasias da Mama/genética
Quimioterapia Adjuvante
Variações do Número de Cópias de DNA
Feminino
Estudos de Associação Genética
Genoma Humano
Mutação em Linhagem Germinativa
Seres Humanos
Mutação INDEL
Meia-Idade
Terapia Neoadjuvante
Polimorfismo de Nucleotídeo Único
Receptor ErbB-2/metabolismo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); P188ANX8CK (Trastuzumab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx048


  8 / 20520 MEDLINE  
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[PMID]:27773872
[Au] Autor:Willmore-Payne C; Damjanovich-Colmenares K; Pasi AV; Werner TL; Gulbahce HE; Downs-Kelly E; Geiersbach KB
[Ad] Endereço:From the ARUP Laboratories, Salt Lake City, UT.
[Ti] Título:Inconsistent Results With Different Secondary Reflex Assays for Resolving HER2 Status.
[So] Source:Am J Clin Pathol;146(5):618-626, 2016 Nov 01.
[Is] ISSN:1943-7722
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: Guidelines suggest that secondary reflex testing may be useful for resolving HER2 status in breast cancers with equivocal results by both immunohistochemistry (IHC) and in situ hybridization (ISH). We compared two reflex ISH assays and a polymerase chain reaction (PCR) assay for this application. Methods: Twenty-nine breast cancers with equivocal IHC and ISH results were retested two ways: (1) ISH using differentially labeled probes targeting ERBB2 ( HER2 , 17q12) and either RAI1 (17p11.2) or ORC4 (2q22.3-2q23.1) in two separate assays and (2) real-time quantitative PCR amplification of ERBB2 and a control locus ( EIF5B , 2q11.2). Results: Results of the HER2 / RAI1 and HER2 / ORC4 ISH assays were concordant for 21 (72%) cases, and results of all three secondary reflex assays were concordant for only 18 (62%) cases. Result discrepancies between the two ISH readers were observed for cases close to the cutoff threshold. Conclusions: Use of different control loci for ISH is associated with discordant results, and PCR is more likely to classify cases as nonamplified, possibly due to contamination with nontumor cells. While resolution of HER2 -equivocal results is desirable from a clinical perspective, different secondary reflex assays yield different results, and the correlation of these results with clinical outcomes is unknown.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Neoplasias da Mama/metabolismo
Receptor ErbB-2/metabolismo
[Mh] Termos MeSH secundário: Neoplasias da Mama/diagnóstico
Neoplasias da Mama/patologia
Proteínas de Ciclo Celular/genética
Proteínas de Ciclo Celular/metabolismo
Feminino
Seres Humanos
Imuno-Histoquímica
Hibridização In Situ
Complexo de Reconhecimento de Origem/genética
Complexo de Reconhecimento de Origem/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Receptor ErbB-2/genética
Reflexo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Cell Cycle Proteins); 0 (ORC4 protein, human); 0 (Origin Recognition Complex); 0 (RAI1 protein, human); 0 (Transcription Factors); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1093/ajcp/aqw177


  9 / 20520 MEDLINE  
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[PMID]:29325268
[Au] Autor:Li MJ; Li HR; Cheng X; Bi R; Tu XY; Liu F; Chen LH
[Ad] Endereço:Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
[Ti] Título:[Clinical significance of targeting drug-based molecular biomarkers expression in ovarian clear cell carcinoma].
[So] Source:Zhonghua Fu Chan Ke Za Zhi;52(12):835-843, 2017 Dec 25.
[Is] ISSN:0529-567X
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues. The positive rates of EGFR, HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs 35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40) vs 17% (4/23) , and there were no significant differences between primary and recurrent OCCC (all 0.05). χ(2)-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance ( 0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all 0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC (4 months vs 10 months, log-rank test, 0.05 for HER2; and 4 months vs 10 months, 0.05 for AURKA); and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, 0.05 for HER2; and 13 months vs 43 months, 0.05 for AURKA). However, multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC ( 0.05). HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.
[Mh] Termos MeSH primário: Adenocarcinoma de Células Claras/tratamento farmacológico
Adenocarcinoma de Células Claras/metabolismo
Biomarcadores Tumorais/metabolismo
Neoplasias Epiteliais e Glandulares/tratamento farmacológico
Neoplasias Epiteliais e Glandulares/metabolismo
Neoplasias Ovarianas/tratamento farmacológico
Neoplasias Ovarianas/metabolismo
Medicina de Precisão
[Mh] Termos MeSH secundário: Adenocarcinoma de Células Claras/diagnóstico
Adenocarcinoma de Células Claras/mortalidade
Proteína BRCA2
China
Intervalo Livre de Doença
Feminino
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Terapia de Alvo Molecular
Recidiva Local de Neoplasia
Neoplasias Epiteliais e Glandulares/diagnóstico
Neoplasias Epiteliais e Glandulares/mortalidade
Neoplasias Ovarianas/diagnóstico
Neoplasias Ovarianas/mortalidade
Receptor do Fator de Crescimento Epidérmico
Receptor ErbB-2
Análise de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BRCA2 Protein); 0 (BRCA2 protein, human); 0 (Biomarkers, Tumor); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-567x.2017.12.008


  10 / 20520 MEDLINE  
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[PMID]:29295986
[Au] Autor:Linde N; Casanova-Acebes M; Sosa MS; Mortha A; Rahman A; Farias E; Harper K; Tardio E; Reyes Torres I; Jones J; Condeelis J; Merad M; Aguirre-Ghiso JA
[Ad] Endereço:Division of Hematology and Oncology, Department of Medicine, Tisch Cancer Institute, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
[Ti] Título:Macrophages orchestrate breast cancer early dissemination and metastasis.
[So] Source:Nat Commun;9(1):21, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2 breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206 /Tie2 macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2 early cancer cells. We also observe macrophage-containing tumor microenvironments of metastasis structures in the pre-malignant lesions that can operate as portals for intravasation. These data support a causal role for macrophages in early dissemination that affects long-term metastasis development much later in cancer progression. A pilot analysis on human specimens revealed intra-epithelial macrophages and loss of E-cadherin junctions in ductal carcinoma in situ, supporting a potential clinical relevance.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
Macrófagos/patologia
[Mh] Termos MeSH secundário: Animais
Progressão da Doença
Feminino
Camundongos
Metástase Neoplásica
Células RAW 264.7
Receptor ErbB-2/genética
Via de Sinalização Wnt
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.7.10.1 (Erbb2 protein, mouse); EC 2.7.10.1 (Receptor, ErbB-2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02481-5



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