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1.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-782226

RESUMO

Lung cancer remains the most common cause of cancer-related deaths worldwide. Although there are many possible treatments, including targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, new therapeutic strategies are needed to improve clinical outcomes. Immunotherapy through the use of immune checkpoint inhibitors has provided one of the most important breakthroughs in the management of solid tumors, including lung cancers, and has shown promising results in numerous clinical trials. This review will present the current status of immunotherapy for lung cancer and future perspectives on these treatments.


Assuntos
Imunoterapia , Neoplasias Pulmonares , Pulmão , Linfoma , Fosfotransferases , Prognóstico , Proteínas Tirosina Quinases , Receptores ErbB
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-782222

RESUMO

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is tested by immunohistochemistry (IHC)—22C3, SP263, and SP142. The aim of this study is to evaluate the correlation among the three methods of PD-L1 IHC in non-small cell lung cancer (NSCLC) and clinical significance of PD-L1 expression in lung adenocarcinoma with an epidermal growth factor receptor (EGFR)–tyrosine kinase domain mutation.METHODS: The results of 230 patients who were pathologically confirmed as having NSCLC; tested using PD-L1 IHC 22C3, SP263, and SP142 methods; and evaluated via the peptide nucleic acid clamping method to confirm EGFR mutation, were analyzed in this study.RESULTS: 164 patients underwent both the SP263 and 22C3 tests. There was a significant positive correlation between the outcomes of the two tests (Spearman correlation coefficient=0.912, p<0.001), with a derived regression equation as follows: 22C3=15.2+0.884×SP263 (R2=0.792, p<0.001). There was no relationship between the expression of PD-L1 and clinical parameters, including EGFR–tyrosine kinase inhibitor (TKI) mutation. The PD-L1 expression in patients treated with EGFR-TKI yielded a 2-month-shorter progression period than that in the PD-L1–negative group. However, this did not reach statistical significance (PD-L1<1% vs. PD-L1≥1%, 10 months vs. 8 months).CONCLUSION: The results of the 22C3 and those of SP263 methods were in good correlation with one another. Since the PD-L1 expression is not influenced by the EGFR mutation, it is necessary to perform a PD-L1 test to set the treatment direction in the patients with EGFR-mutant NSCLC.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Constrição , Humanos , Imuno-Histoquímica , Pulmão , Métodos , Fosfotransferases , Receptores ErbB
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-782110

RESUMO

OBJECTIVE: To determine the added value of a shear-wave elastography (SWE) quality map (QM) in the diagnosis of breast lesions and in predicting the biological characteristics of invasive breast cancer.MATERIALS AND METHODS: Between January 2016 and February 2019, this study included 368 women with 368 pathologically proven breast lesions, which appeared as poor-quality regions in the QM of SWE. To measure shear-wave velocity (SWV), seven regions of interest were placed in each lesion with and without QM guidance. Under QM guidance, poor-quality areas were avoided. Diagnostic performance was calculated for mean SWV (SWV(mean)), max SWV (SWV(max)), and standard deviation (SD) with QM guidance (SWV(mean) + QM, SWV(max) + QM, and SD + QM, respectively) and without QM guidance (SWV(mean) − QM, SWV(max) − QM, and SD − QM, respectively). For invasive cancers, the relationship between SWV findings and biological characteristics was investigated with and without QM guidance.RESULTS: Of the 368 women (mean age, 47 years; SD, 10.8 years) enrolled, 159 had benign breast lesions and 209 had malignant breast lesions. SWV(mean) + QM (3.6 ± 1.39 m/s) and SD + QM (1.02 ± 0.84) were significantly different from SWV(mean) − QM (3.29 ± 1.22 m/s) and SD − QM (1.46 ± 1.06), respectively (all p < 0.001). For differential diagnosis of breast lesions, the sensitivity and areas under the receiver operating characteristic curve (AUC) of SWV(mean) + QM (sensitivity: 89%; AUC: 0.932) were better than those of SWV(mean) − QM (sensitivity, 84.2%; AUC, 0.912) (all p < 0.05). There was no significant difference in sensitivity and specificity between SD + QM and SD − QM (all p = 1.000). Among the biological characteristics of invasive cancers, lymphovascular involvement, axillary lymph node metastasis, negative estrogen receptor status, negative progesterone receptor status, positive human epidermal growth factor receptor status, and aggressive molecular subtypes showed higher SWV(mean) + QM (all p < 0.05), while only lymphovascular involvement showed higher SWV(mean) − QM (p = 0.036).CONCLUSION: The use of QM in SWE might improve the diagnostic performance for breast lesions and facilitate prediction of the biological characteristics of invasive breast cancers.


Assuntos
Área Sob a Curva , Neoplasias da Mama , Mama , Diagnóstico , Diagnóstico Diferencial , Técnicas de Imagem por Elasticidade , Estrogênios , Feminino , Humanos , Linfonodos , Metástase Neoplásica , Características da População , Receptores ErbB , Receptores de Progesterona , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-811195

RESUMO

PURPOSE: Aberrant glycosylation of the histo-blood group antigens (including the angina bullosa haemorrhagica [ABH]) is often observed during malignant transformation in most types of carcinomas. Data concerning their ethnic distributions are diverse which explains why their biological characteristics have to be studied in different populations. Our aim was to analyze the expression of the histo-blood group (specifically the ABH) antigens in breast carcinoma.METHODS: The expression of the histo-blood group (specifically the ABH) antigens was studied in 109 patients with breast carcinoma using immunohistochemistry. Statistical analysis was performed using χ² and Fisher analyses.RESULTS: The loss of expression of histo-blood group (ABH) antigens in breast carcinoma was observed in 81.13% of patients with blood group O, 37.93% with blood group A, and 96.30% with blood group B. One key finding of this study was that the loss of expression of the ABH antigen was also observed in normal tissues adjacent to the tumor. The loss of expression was associated with higher tumor grade (p < 0.05). Expression of H antigen was observed in 50% of cases with loss of expression of B antigen and was associated with human epidermal growth factor receptor 2 (HER2) overexpression (p < 0.05). The loss of H antigen in patients with blood group O was associated with estrogen receptor expression (p < 0.001). Incompatible A antigen in tumor was expressed in 20.75% of patients with blood group O.CONCLUSION: Loss of the ABH antigens correlated with the Scarff-Bloom-Richardson histologic grading. H antigen was associated with HER2 overexpression in breast cancer. However, further studies are needed to determine the role of incompatible A antigen in mammary carcinogenesis.


Assuntos
Neoplasias da Mama , Mama , Carcinogênese , Estrogênios , Glicosilação , Histocompatibilidade , Humanos , Imuno-Histoquímica , Características da População , Receptores ErbB
5.
Braz. dent. sci ; 23(3): 1-7, 2020. tab, graf
Artigo em Inglês | LILACS (Américas), BBO | ID: biblio-1116017

RESUMO

Objective: κ-carrageenan is a food stabilizer agent which has an antiproliferative effect, while vitamin D is a prohormone acts on the nuclear receptor and has a cytotoxic against cancer. This study aimed to show the synergistic effect of using topical κ-carrageenan and oral administration of the vitamin D on the 7, 12-dimethylbenz[a] anthracene (DMBA)-induced oral cancer. Material and Methods: fifty four male albino rats were randomly divided into seven groups: Acetonetreated served as control (Group I), vitamin D (5000UI)-treated (Group II), κ-carrageenan (1%)- treated (Group III), DMBA (0.5%)-treated (Group IV), Acetone, κ-carrageenan and DMBA were administered topically on both cheeks and palate, five times weekly for 12 weeks, while the vitamin D was administered orally twice weekly for 12 weeks. Groups V, VI, and VII were animals treated with vitamin D, κ-carrageenan, and both vitamin D and κ-carrageenan for 8 weeks after induction of oral cancer. At the end of the study, blood samples were obtained by cardiac puncture for determination of TNF-α and EGFR. Results: In the groups III and IV, serum EGFR showed significant low levels compared with Group I. In the Group VII, serum EGFR showed a significantly (p=0.014) low level compared with Group IV (614.3±69.7 pg/ml versus 882.4±45.6 pg/ml, respectively). Higher percentages of high levels of TNF-α were observed in the Groups VI and VII, while a lower percentage of EGFR was observed in the Group VI. Conclusion: both κ-carrageenan and vitamin D have antiproliferative effect against DMBAinducing oral cancer by increasing the levels of TNF-α and suppressing the signaling pathway of EGFR. Concomitant using κ-carrageenan and vitamin D reduces the antiproliferative effect of each other.(AU)


Objetivo: κ-carragenina é um agente estabilizador de alimentos que tem efeito um antiproliferativo, enquanto a vitamina D é um pró-hormônio que atua sobre o receptor nuclear e possui efeito citotóxico contra o câncer. Este estudo teve como objetivo mostrar o efeito sinérgico do uso de κ-carragenina tópica e administração oral da vitamina D no câncer de boca induzido por 7, 12-dimetilbenz[a]antraceno (DMBA). Material e Métodos: cinquenta e quatro ratos albinos machos foram divididos aleatoriamente em sete grupos: tratado com acetona como controle (Grupo I), tratado com vitamina D (5000UI) (grupo II), tratado com κ-carragenina (1%) (grupo III), DMBA (0,5%) tratado (Grupo IV), acetona, κ-carragenina e DMBA foram administrados topicamente nas bochechas e no palato, cinco vezes por semana durante 12 semanas, enquanto a vitamina D foi administrada por via oral duas vezes por semana durante 12 semanas. Os grupos V, VI e VII foram animais tratados com vitamina D, κ-carragenina e No final do estudo, foram obtidas amostras de sangue por punção cardíaca para determinação do TNF-α e EGFR. Resultados: Nos grupos III e IV, o EGFR sérico mostrou níveis baixos significativos em comparação com o Grupo I. No grupo VII, o EGFR sérico mostrou um nível significativamente baixo (p = 0,014) em comparação com o Grupo IV (614,3 ± 69,7 pg / ml versus 882,4 ± 45,6 pg / ml, respectivamente). Maiores porcentagens de TNF-α foram observadas nos Grupos VI e VII, enquanto uma menor porcentagem de EGFR foi observada no Grupo VI. Conclusão: Tanto a κ-carragenina quanto a vitamina D têm efeito antiproliferativo contra o câncer de boca induzido por DMBA aumentando os níveis de TNF-α e suprimindo a via de sinalização do EGFR. O uso concomitante de κ-carragenina e a vitamina D reduz o efeito antiproliferativo um do outro (AU)


Assuntos
Animais , Ratos , Vitamina D , Neoplasias Bucais , Fator de Necrose Tumoral alfa , 9,10-Dimetil-1,2-benzantraceno , Receptores ErbB
6.
Chinese Medical Journal ; (24): 454-465, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-774832

RESUMO

BACKGROUND@#Long noncoding RNAs (lncRNAs) play pivotal roles in various malignant tumors. Epidermal growth factor receptor (EGFR) signaling is associated with the pathogenesis of cutaneous squamous cell carcinoma (cSCC). This study aimed to explore the role of LINC00520 in the development of cSCC via EGFR and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways.@*METHODS@#A microarray analysis was applied to screen differentially expressed lncRNAs in cSCC samples. The A431 cSCC cell line was transfected and assigned different groups. The expression patterns of LINC00520, EGFR, and intermediates in the PI3K/Akt pathway were characterized using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis. Cell proliferation, migration, and invasion were detected using the MTT assay, scratch test, and Transwell assay, respectively. Cell-based experiments and a tumorigenicity assay were conducted to assess the effect of LINC00520 on cSCC progression. This study was ended in September 2017. Comparisons between two groups were analyzed with t-test and comparisons among multiple groups were analyzed using one-way analysis of variance. The nonparametric Wilcoxon rank sum test was used to analyze skewed data. The enumerated data were analyzed using the chi-square test or Fisher exact test.@*RESULTS@#Data from chip GSE66359 revealed depletion of LINC00520 in cSCC. Cells transfected with LINC00520 vector and LINC00520 vector + si-EGFR showed elevated LINC00520 level but decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the si-LINC00520 group showed opposite trends (all P < 0.05). Compared with the LINC00520 vector group, the LINC00520 vector + si-EGFR group showed decreased levels of the EGFR, PI3K, AKT, VEGF, MMP-2 and MMP-9 mRNAs and proteins, and inhibition of the growth, migration and adhesion of cSCC cells, while the LINC00520 vector + EGFR vector group showed opposite results (all P < 0.05).@*CONCLUSION@#Based on our results, LINC00520-targeted EGFR inhibition might result in the inactivation of the PI3K/Akt pathway, thus inhibiting cSCC development.


Assuntos
Animais , Carcinoma de Células Escamosas , Patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Receptores ErbB , Feminino , Humanos , Metástase Linfática , Camundongos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases , Fisiologia , Proteínas Proto-Oncogênicas c-akt , Fisiologia , RNA Longo não Codificante , Fisiologia , Transdução de Sinais , Fisiologia , Neoplasias Cutâneas , Patologia
7.
Yonsei Medical Journal ; : 509-516, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762085

RESUMO

PURPOSE: This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). MATERIALS AND METHODS: Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by WST-1 assay, Hemacolor staining, Hoechst staining, immunofluorescence staining, fluorescence-activated cell sorting analysis, and Western blotting.


Assuntos
Actinas , Fator de Indução de Apoptose , Apoptose , Western Blotting , Caspase 3 , Caspases , Adesão Celular , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Morte Celular , Ciclina A , Ciclina D1 , Ciclina E , Ciclinas , Citocromos c , Citoplasma , Fragmentação do DNA , Regulação para Baixo , Citometria de Fluxo , Imunofluorescência , Adesões Focais , Melanoma , Mitocôndrias , Nanopartículas , Fosfotransferases , Receptores ErbB , Regulação para Cima
8.
Yonsei Medical Journal ; : 525-534, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762083

RESUMO

PURPOSE: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC. MATERIALS AND METHODS: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy. RESULTS: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively. CONCLUSION: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.


Assuntos
Broncoscopia , Carcinoma Pulmonar de Células não Pequenas , Estudos de Coortes , Intervalo Livre de Doença , Resistência a Medicamentos , Humanos , Incidência , Modelos Estatísticos , Fosfotransferases , Plasma , Receptores ErbB , Resultado do Tratamento
9.
Yonsei Medical Journal ; : 1028-1035, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762057

RESUMO

PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer—Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.


Assuntos
Biópsia , Neoplasias da Mama , Mama , Calibragem , Carcinoma Ductal , Carcinoma Intraductal não Infiltrante , Estudos de Coortes , Discriminação Psicológica , Humanos , Modelos Logísticos , Registros Médicos , Métodos , Análise Multivariada , Necrose , Nomogramas , Patologia , Receptores ErbB , Fatores de Risco , Curva ROC , Ultrassonografia
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772003

RESUMO

OBJECTIVE@#To establish a rapid and accurate "on/off" switch technique consisted of 3'-phosphorothioate-modified allele-specific primers and exo+ polymerase to screen the G719S and T790M mutations of epidermal growth factor receptor (EGFR) gene. The switch was used to identify cervical cancer patients who are sensitive to tyrosine kinase inhibitor (TKI).@*METHODS@#Allele-specific primers targeting recombinant wild-type and mutation-type templates were designed with 3' terminal phosphorothioate modification. Two-directional primer extension was carried out using Pfu polymerase. The G719S and T790M mutations were detected by the technique among cervical cancer tissues. The results were verified by Sanger sequencing.@*RESULTS@#No mutation was detected among the 80 cervical cancer cases, and the results were consistent with that of Sanger sequencing. No significant difference was found between the frequencies of the G719S and T790M mutations between the patient and the control groups (P> 0.05).@*CONCLUSION@#A sensitive "on/off" switch technique for detecting the two EGFR mutations was established. The G719S and T790M mutations are not associated with cervical cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Genética , Feminino , Genes erbB-1 , Humanos , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Neoplasias do Colo do Útero , Genética
11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-788064

RESUMO

PURPOSE: The objective of this study was to investigate the outcomes of selected patients with stomach cancer liver metastasis (SCLM) without extrahepatic metastases after hepatic resection.METHODS: Patients whose imaging results did not detect extrahepatic disease were selected for hepatic resection. If R0 resection was possible and if the operative risk was low in the preoperative tests, the patients underwent hepatic resection.RESULTS: Between 2011 and 2016, seven patients underwent hepatic resection for SCLM. All patients received hepatic resection to achieve an R0 resection. Minor liver resection was performed in all patients. Two patients showed long-term survival with a single lesion and human epidermal growth factor receptor 2 (HER2)-negative tumor. The 5-year overall survival and disease-free survival rates after hepatic resection were 38.1% and 28.6%, respectively.CONCLUSION: Hepatic resection for isolated SCLM may be considered as a multimodality treatment. However, it has only limited benefits in select patients. It has long-term survival benefit in patients with single metastases and HER2-negative hormonal status.


Assuntos
Intervalo Livre de Doença , Humanos , Fígado , Metástase Neoplásica , Receptores ErbB , Neoplasias Gástricas , Estômago
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-739582

RESUMO

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.


Assuntos
Área Sob a Curva , Neoplasias da Mama , Mama , Calibragem , Discriminação Psicológica , Tratamento Farmacológico , Humanos , Modelos Logísticos , Linfonodos , Terapia Neoadjuvante , Metástase Neoplásica , Nomogramas , Reação em Cadeia da Polimerase , Receptores ErbB , Receptores de Progesterona
13.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-739142

RESUMO

BACKGROUND: Plasma epidermal growth factor receptor (EGFR) mutation tests are less invasive than tissue EGFR mutation tests. We determined which of two kits is more efficient: cobas EGFR Mutation test v2 (cobasv2; Roche Molecular Systems, Pleasanton, CA, USA) or PANAMutyper-R-EGFR (Mutyper; Panagene, Daejeon, Korea). We also evaluated whether pleural effusion supernatant (PE-SUP) samples are assayable, similar to plasma samples, using these two kits. METHODS: We analyzed 156 plasma and PE-SUP samples (31 paired samples) from 116 individuals. We compared the kits in terms of accuracy, assessed genotype concordance (weighted κ with 95% confidence intervals), and calculated Spearman's rho between semi-quantitatively measured EGFR-mutant levels (SQIs) measured by each kit. We also compared sensitivity using 47 EGFR-mutant harboring samples divided into more-dilute and less-dilute samples (dilution ratio: ≥ or <1:1,000). RESULTS: cobasv2 tended to have higher accuracy than Mutyper (73% vs 69%, P=0.53), and PE-SUP samples had significantly higher accuracy than plasma samples (97% vs 55–71%) for both kits. Genotype concordance was 98% (κ=0.92, 0.88–0.96). SQIs showed strong positive correlations (P<0.0001). In less-dilute samples, accuracy and sensitivity did not differ significantly between kits. In more-dilute samples, cobasv2 tended to have higher sensitivity than Mutyper (43% vs 20%, P=0.07). CONCLUSIONS: The kits have similar performance in terms of EGFR mutation detection and semi-quantification in plasma and PE-SUP samples. cobasv2 tends to outperform Mutyper in detecting less-abundant EGFR-mutants. PE-SUP samples are assayable using either kit.


Assuntos
Fator de Crescimento Epidérmico , Genótipo , Plasma , Derrame Pleural , Receptores ErbB
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-738415

RESUMO

PURPOSE: The Z0011 trial showed that axillary lymph node dissection (ALND) can be safely avoided in breast cancer patients with low nodal burden (LNB). ALND can be performed in patients with high nodal burden (HNB). We aimed to determine whether HNB in early breast cancer patients can be predicted preoperatively to avoid sentinel lymph node biopsy (SLNB). METHODS: Early invasive breast cancer patients (cT1-2cN0) were retrospectively reviewed. We excluded patients with neoadjuvant chemotherapy and incomplete data. The patients were divided into the following groups based on surgical histology: no positive (N0), LNB, and HNB, defined as 0, 1–2, and ≥ 3 metastatic lymph nodes (LNs), respectively. Of the patients with metastatic nodal disease, only those with ALND were included in the analysis. Clinical, radiological, and histological parameters were evaluated using logistic regression analysis as predictors of HNB versus LNB and N0 combined. RESULTS: Of the 1,298 included patients, 832 (64.1%), 286 (22.0%), and 180 (13.9%) had N0, LNB, and HNB, respectively. Univariate logistic regression analysis revealed that sonographic features of breast tumor size (p < 0.0001), number of abnormal LNs (p < 0.0001), cortical thickness (p = 0.0002), effacement of the fatty hilum (p < 0.0001), and needle biopsy being performed (p < 0.0001) were indicators of HNB. Breast tumor grade (p = 0.0001) and human epidermal growth factor receptor 2 status (p = 0.0262) were also statistically significant. Among these significant features, multivariable stepwise logistic regression showed that the number of abnormal LNs is the sole independent predictor of HNB (p < 0.0001, area under the curve = 0.774). The positive predictive value of HNB in patients with ≥ 4 abnormal LNs was 92.9%. CONCLUSION: The detection of ≥ 4 abnormal LNs on ultrasound can help to identify HNB patients who require upfront ALND and thus avoid SLNB.


Assuntos
Biópsia por Agulha , Neoplasias da Mama , Mama , Tratamento Farmacológico , Humanos , Modelos Logísticos , Excisão de Linfonodo , Linfonodos , Receptores ErbB , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Ultrassonografia
15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-738414

RESUMO

PURPOSE: We investigated the prognostic significance of CD9 expression in tumor cells of patients with invasive lobular carcinoma (ILC). METHODS: CD9 expression was evaluated by immunohistochemistry in 113 ILC tissue samples. Correlation of CD9 expression with the patients' clinicopathological parameters and overall survival was assessed. RESULTS: CD9 expression was detected in 48 (42.5%) ILC patients. However, no significant relation could be determined between CD9 expression and the clinicopathological parameters of the patient including tumor size, lymph node metastasis, lymphovascular invasion, histologic grade, expression of hormone receptors, human epidermal growth factor receptor 2 status, and Ki-67 labeling index. Patients with CD9 expression had worse overall survival (p = 0.051) and disease-free survival (DFS, p = 0.014) compared to patients without CD9 expression. Multivariate analysis revealed that CD9 expression was an independent prognostic factor for DFS (p = 0.049). CONCLUSION: CD9 expression in tumor cells could be a significant prognostic marker in patients with ILC.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Linfonodos , Análise Multivariada , Metástase Neoplásica , Prognóstico , Receptores ErbB
16.
Journal of Breast Cancer ; : 120-130, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-738410

RESUMO

PURPOSE: The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). METHODS: A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). RESULTS: The median follow-up duration was 84 (range, 8–171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076–4.746; p = 0.031). CONCLUSION: Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.


Assuntos
Encéfalo , Neoplasias da Mama , Mama , Neoplasias do Sistema Nervoso Central , Sistema Nervoso Central , Quimioterapia Adjuvante , Intervalo Livre de Doença , Tratamento Farmacológico , Seguimentos , Humanos , Mastectomia , Análise Multivariada , Metástase Neoplásica , Qualidade de Vida , Radioterapia (Especialidade) , Radioterapia , Receptores ErbB , Estudos Retrospectivos , Taxa de Sobrevida , Trastuzumab
17.
Yonsei Medical Journal ; : 158-162, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-742523

RESUMO

PURPOSE: Trastuzumab is an effective treatment for human epidermal growth factor receptor 2 (HER2)-amplified breast cancers. We sought to develop a simple protocol for HER2 image analysis of breast cancer specimens. MATERIALS AND METHODS: In a preliminary test, we found that at least 1000 tumor cells need to be examined in the most strongly stained areas. Next, we evaluated the clinical usefulness of this established protocol of image analysis in 555 breast cancer patients. Results of the HER2 immunohistochemical (IHC) staining were compared between manual scoring and image analysis. RESULTS: The HER2 IHC results obtained by the image analysis method correlated well with those obtained by the manual scoring method (Cohen's kappa=0.830). Using the HER2 silver in situ hybridization (SISH) results as a gold standard, sensitivity values were 72.1% for manual scoring and 74.0% for image analysis; specificity values were 96.2% for manual scoring and 94.7% for image analysis; and accuracy values were 91.7% for manual scoring and 90.8% for image analysis. McNemar's test was applied to the results, and there were no statistically significant differences in sensitivity and specificity between the positive (p=0.688) and negative (p=0.118) SISH groups. CONCLUSION: HER2 image analysis results were similar to those obtained via the manual scoring method, indicating that the use of image analysis can reduce assessment time and effort. We suggest that image analysis-based evaluation of 1000 tumor cells in the most strongly IHC-stained area, regardless of stroma content, is sufficient for determining HER2 expression levels in breast cancer specimens.


Assuntos
Neoplasias da Mama , Mama , Humanos , Imuno-Histoquímica , Hibridização In Situ , Métodos , Receptores ErbB , Projetos de Pesquisa , Sensibilidade e Especificidade , Prata , Trastuzumab
18.
Journal of Breast Disease ; (2): 30-37, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-764286

RESUMO

PURPOSE: We aimed to investigate organ-specific recurrence or the metastatic pattern of breast cancer according to biological subtypes and clinical characteristics. METHODS: We retrospectively analyzed the medical records of 168 patients with recurrent breast cancer who were diagnosed between January 1, 2000 and April 30, 2017. Four biological subtypes were classified according to estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 expression: luminal A, luminal B, HER2-enriched, and triple negative breast cancer (TNBC). To analyze recurrence patterns according to biological subtypes, we accessed clinical variables including age at diagnosis, TNM stage, type of surgery in the breast and axilla, histologic grade, nuclear grade, lymphatic, vascular, and neural invasion, Ki-67 expression and recurrence to distant organs. RESULTS: The biological subtypes of recurrent breast cancer comprised the following luminal A (n=33, 19.6%), luminal B (n=95, 56.5%), HER2 enriched (n=19, 11.3%), and TNBC (n=21, 12.5%). Luminal A (7.7%) and B (6.5%) subtypes were associated with the increased rate of local recurrence compared to HER2-enriched (2.4%) and TNBC subtypes (1.8%) (p=0.005). The bone (53.6%) was the most common metastatic organ, followed by the lung (34.5%), liver (29.8%), brain (17.9%), and other visceral organ (7.7%). Bone metastasis was commonly observed in individuals with luminal B (63.2%), HER2-enriched (57.9%), and luminal A (42.4%) subtypes (p=0.005). Most liver metastases occur in individuals with luminal B (40.0%) and HER2-enriched subtypes (31.6%) (p=0.002). CONCLUSION: Luminal B subtype was commonly observed in individuals with recurrent breast cancer, and the bone is the most common target organ for breast cancer metastasis, followed by the lungs and liver.


Assuntos
Axila , Encéfalo , Neoplasias da Mama , Mama , Diagnóstico , Estrogênios , Humanos , Fígado , Pulmão , Registros Médicos , Metástase Neoplásica , Especificidade de Órgãos , Fenobarbital , Receptores ErbB , Receptores de Progesterona , Recidiva , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas
19.
Journal of Breast Cancer ; : 341-361, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-764285

RESUMO

Breast cancer (BC) is still the most common cancer among women worldwide. Amongst the subtypes of BC, triple negative breast cancer (TNBC) is characterized by deficient expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. These patients are therefore not given the option of targeted therapy and have worse prognosis as a result. Consequently, much research has been devoted to identifying specific molecular targets that can be utilized for targeted cancer therapy, thereby limiting the progression and metastasis of this invasive tumor, and improving patient outcomes. In this review, we have focused on the molecular targets in TNBC, categorizing these into targets within the immune system such as immune checkpoint modulators, intra-nuclear targets, intracellular targets, and cell surface targets. The aim of this review is to introduce and summarize the known targets and drugs under investigation in phase II or III clinical trials, while introducing additional possible targets for future drug development. This review brings a tangible benefit to cancer researchers who seek a comprehensive comparison of TNBC treatment options.


Assuntos
Neoplasias da Mama , Tratamento Farmacológico , Estrogênios , Feminino , Humanos , Sistema Imunitário , Metástase Neoplásica , Progesterona , Prognóstico , Receptores ErbB , Neoplasias de Mama Triplo Negativas
20.
Journal of Breast Cancer ; : 412-424, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-764280

RESUMO

PURPOSE: Neoadjuvant chemotherapy (NAC) is less effective for luminal breast cancer because luminal breast cancer has a lower rate of pathological complete response (pCR) after NAC than human epidermal growth factor receptor 2 (HER2)-type and triple-negative breast cancer (TNBC). We investigated the efficacy of NAC and the predictive factors of a better response in luminal breast cancer. METHODS: Between 2010 and 2016, we retrieved data of 244 patients with clinically node-positive breast cancer who were treated with NAC followed by surgery from a prospectively collected database. We classified breast cancer into luminal HER2⁻ and non-luminal HER2⁻ breast cancer (luminal HER2⁺, HER2⁺, and TNBC types). We analyzed each subtype with respect to surgical outcomes, response to NAC, and determined variables associated with surgical outcomes and response in patients with luminal HER2⁻ breast cancer. RESULTS: The total, breast, and axillary pCR rates were significantly lower in 114 patients with luminal HER2⁻ breast cancer than in those with other subtypes (7.9%, 12.3%, and 22.8%, respectively). However, breast-conserving surgery (BCS) conversion and tumor response rates did not significantly differ between patients with luminal HER2⁻ and those with non-luminal HER2⁻ breast cancer (p = 0.836 and p = 0.180, respectively). In the multivariate analysis, high tumor response rate (≥ 46.4%) was significantly associated with an increased BCS conversion rate. In the subgroup analysis of luminal HER2⁻ breast cancer, the multivariate analysis showed that higher Ki67 expression and axilla pCR and BCS conversion rates were significantly associated with tumor response to NAC. CONCLUSION: Despite the low pCR rate, the tumor response and BCS conversion rates after NAC of luminal HER2⁻ breast cancer were similar to those of other subtypes. NAC has the potential benefit of reducing the size of breast cancer, thereby increasing the BCS conversion rate in luminal HER2⁻ breast cancer.


Assuntos
Axila , Neoplasias da Mama , Mama , Tratamento Farmacológico , Humanos , Mastectomia Segmentar , Análise Multivariada , Terapia Neoadjuvante , Fenobarbital , Reação em Cadeia da Polimerase , Estudos Prospectivos , Receptores ErbB , Neoplasias de Mama Triplo Negativas
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