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1.
Ann Surg Treat Res ; 106(5): 263-273, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38725802

RESUMO

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion: This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

2.
Expert Opin Biol Ther ; 24(4): 305-312, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38664937

RESUMO

BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.


Assuntos
Antineoplásicos Imunológicos , Medicamentos Biossimilares , Neoplasias da Mama , Vigilância de Produtos Comercializados , Neoplasias Gástricas , Trastuzumab , Humanos , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Trastuzumab/efeitos adversos , Trastuzumab/uso terapêutico , República da Coreia , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Mama/tratamento farmacológico , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Idoso , Masculino , Neoplasias Gástricas/tratamento farmacológico , Receptor ErbB-2/genética , Resultado do Tratamento , Idoso de 80 Anos ou mais
3.
Biomedicines ; 12(1)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38255277

RESUMO

Breast cancer, with its global prevalence and impact on women's health, necessitates effective early detection and accurate staging for optimal patient outcomes. Traditional imaging modalities such as mammography, ultrasound, and dynamic contrast-enhanced magnetic resonance imaging (MRI) play crucial roles in local-regional assessment, while bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aid in evaluating distant metastasis. Despite the proven utility of 18F-FDG PET/CT in various cancers, its limitations in breast cancer, such as high false-negative rates for small and low-grade tumors, have driven exploration into novel targets for PET radiotracers, including estrogen receptor, human epidermal growth factor receptor-2, fibroblast activation protein, and hypoxia. The advent of PET/MRI, which combines metabolic PET information with high anatomical detail from MRI, has emerged as a promising tool for breast cancer diagnosis, staging, treatment response assessment, and restaging. Technical advancements including the integration of PET and MRI, considerations in patient preparation, and optimized imaging protocols contribute to the success of dedicated breast and whole-body PET/MRI. This comprehensive review offers the current technical aspects and clinical applications of PET/MRI for breast cancer. Additionally, novel targets in breast cancer for PET radiotracers beyond glucose metabolism are explored.

4.
Nutr Cancer ; 76(1): 42-54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37943034

RESUMO

We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60-2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67-0.98) for recurrence and 0.85 (0.76-0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation.


Assuntos
Neoplasias da Mama , Isoflavonas , Humanos , Feminino , Estudos Prospectivos , Modelos de Riscos Proporcionais , Sobreviventes , Fatores de Risco
5.
Oncology ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37899039

RESUMO

INTRODUCTION: SB3 is a trastuzumab biosimilar approved in Australia, Brazil, Canada, the European Union, the Republic of Korea, Switzerland, and the United States. This real-world study evaluated safety and effectiveness of SB3 as part of the Korean post approval safety management system. METHODS: This post-marketing surveillance in Korea included patients in line with approved indications, i.e. patients with early or metastatic breast cancer or metastatic gastric cancer. Safety outcomes were adverse events and adverse drug reactions. Effectiveness outcomes were tumor response and event-free survival. RESULTS: 424 patients were evaluated: 366 patients (86%) with early breast cancer, 53 patients (13%) with metastatic breast cancer, and 5 patients (1%) with metastatic gastric cancer. Among patients with breast cancer, adverse events (mostly mild) and adverse drug reactions were reported by 158 (37.7%) and 57 (13.6%) patients, respectively. Most patients with an AE (141, 75.9%) had no change in treatment schedule. Treatment was temporarily suspended in 14 (8.2%) patients with an AE and completely discontinued in 7 (3.7%). Among patients with early and metastatic breast cancer who were evaluated for efficacy, objective response rates were 82.7% and 38.3%, respectively. Pathological complete response was 64.6% in patients with early breast cancer. DISCUSSION/CONCLUSION: Safety and efficacy of SB3 demonstrated in this real-world study were comparable with previous studies of reference trastuzumab.

6.
Plast Reconstr Surg ; 152(1): 39-43, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36688630

RESUMO

SUMMARY: With the emergence of state-of-the art implant technology and advanced surgical techniques, plastic surgeons face challenging problems, such as identification of a specific type of a device and diagnosis of postoperative complications, in managing patients undergoing implant-based augmentation mammaplasty. In this article, the authors introduce a novel method for characterizing a breast implant based on diverse factors (eg, filler properties, type of pocket, surface topography, shape type, and manufacturer of the device) and detecting the presence and scope of rupture using high-resolution ultrasound.


Assuntos
Implante Mamário , Implantes de Mama , Mamoplastia , Feminino , Humanos , Implantes de Mama/efeitos adversos , Implante Mamário/métodos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Complicações Pós-Operatórias/etiologia , Ultrassonografia , Reoperação/métodos
7.
Ann Surg Treat Res ; 103(4): 183-194, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36304189

RESUMO

Purpose: The prognostic value of vitamin D receptor gene (VDR) expression in breast cancer development is unclear. Here, we aimed to investigate whether VDR expression can be used as a prognostic indicator of breast cancer. Methods: We used various public bioinformatics platforms: Oncomine, GEPIA, UALCAN, Kaplan-Meier plotter, UCSC XENA, bc-GenExMiner, WebGestalt, and STRING database. Results: We found that VDR was upregulated in breast cancer in comparison to normal tissues. Overexpression of VDR was significantly associated with worse overall survival in breast cancer. The expression of VDR was related to age, TNM stages, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, basal-like (PAM 50) status, triple-negative breast cancer (TNBC) status, and basal-like (PAM 50) & TNBC status (P < 0.05). Increased VDR expression in breast cancer was significantly associated with older age. The 5 hub genes for VDR were NCOA1, EP300, CREBBP, and RXRA. Conclusion: Our investigation offers hints about the prognostic role of VDR in breast cancer. The findings suggest that VDR expression might be used as a marker to determine a breast cancer patient's prognosis. Nevertheless, further validation is warranted.

8.
Ann Surg Treat Res ; 103(2): 63-71, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36017142

RESUMO

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients. Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features: T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion: FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

9.
Int J Mol Sci ; 23(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35409110

RESUMO

BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan−Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.


Assuntos
Proteína BRCA2/genética , Biomarcadores Tumorais , Neoplasias da Mama , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Genes BRCA2 , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
10.
Diagnostics (Basel) ; 12(3)2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35328247

RESUMO

This study investigated the prognostic value of FDG PET/CT radiomic features for predicting recurrence in patients with early breast invasive ductal carcinoma (IDC). The medical records of consecutive patients who were newly diagnosed with primary breast IDC after curative surgery were reviewed. Patients who received any neoadjuvant treatment before surgery were not included. FDG PET/CT radiomic features, such as a maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), skewness, kurtosis, entropy, and uniformity, were measured for the primary breast tumor using LIFEx software to evaluate recurrence-free survival (RFS). A total of 124 patients with early breast IDC were evaluated. Eleven patients had a recurrence (8.9%). Univariate survival analysis identified large tumor size (>2 cm, p = 0.045), high Ki-67 expression (≥30%, p = 0.017), high AJCC prognostic stage (≥II, p = 0.044), high SUVmax (≥5.0, p = 0.002), high MTV (≥3.25 mL, p = 0.044), high TLG (≥10.5, p = 0.004), and high entropy (≥3.15, p = 0.003) as significant predictors of poor RFS. After multivariate survival analysis, only high MTV (p = 0.045) was an independent prognostic predictor. Evaluation of the MTV of the primary tumor by FDG PET/CT in patients with early breast IDC provides useful prognostic information regarding recurrence.

11.
Aesthetic Plast Surg ; 46(4): 1668-1678, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35296929

RESUMO

BACKGROUND: We previously proposed a novel method for detecting a rupture of a breast implant using high-resolution ultrasound (HRUS). We therefore conducted this retrospective, observational study to describe its feasibility in making a preoperative diagnosis of rupture of the device in patients receiving an implant-based augmentation mammaplasty. METHODS: We initially evaluated the medical records of the patients who had received primary or secondary augmentation mammaplasty using a breast implant at other hospitals for aesthetic or reconstructive purposes between August 31, 2017, and August 31, 2020. The patients underwent breast US using the Aplio i600 (Canon Medical System, Otawara, Tochigi, Japan) system with a 7-18 MHz linear transducer. Through a retrospective review of the patients' medical records, we analyzed their baseline and clinical characteristics. Then, we compared an agreement between preoperative diagnosis of rupture on HRUS and findings at reoperation. RESULTS: A total of 29 patients with rupture (55 breasts) were evaluated for the performance of ultrasound in making a diagnosis of rupture. This showed that they were unaware of rupture but they were diagnosed with it on ultrasound. Preoperatively, there were no cases of rupture in 110 left breasts (80.9%) and 107 right breasts (78.7%), which exactly matched to the number of breasts without rupture on HRUS. Moreover, preoperatively, there were 26 (19.1%) and 29 cases (21.3%) of rupture in the left and right breast, respectively, which exactly matched to the number of breasts with rupture on HRUS. CONCLUSIONS: In conclusion, patients who are suspected of having rupture of a breast implant should be stringently evaluated for presence of rupture and, if any, its scope using HRUS. Moreover, we propose that surgeons consider using HRUS in making a preoperative diagnosis of rupture of a breast implant. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Implante Mamário , Implantes de Mama , Mamoplastia , Cirurgiões , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Implantes de Mama/efeitos adversos , Remoção de Dispositivo/métodos , Estética , Feminino , Seguimentos , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Falha de Prótese , Estudos Retrospectivos , Resultado do Tratamento
12.
J Pathol Transl Med ; 56(2): 73-80, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35051326

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism-related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC. METHODS: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0-1+ FASN staining were grouped as low-grade FASN and patients with 2-3+ FASN staining as high-grade FASN. RESULTS: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups. CONCLUSIONS: We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

13.
Aesthetic Plast Surg ; 46(3): 1135-1142, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35022838

RESUMO

BACKGROUND: We conducted this study to describe the feasibility of high-resolution ultrasound (HRUS) in characterizing a breast implant in patients receiving an implant-based augmentation mammaplasty. METHODS: The current study was conducted in a total of 612 patients (n =6 12) receiving an implant-based augmentation mammaplasty at other hospitals between August 31, 2017 and August 31, 2020. Of these, 136 patients (n = 136; 272 breasts) receiving reoperation were included in the current study. We compared between the patients' subjective awareness of a breast implant and its HRUS findings and an agreement between HRUS findings of a breast implant and its findings at reoperation. RESULTS: The proportion of the patients receiving a silicone gel-filled breast implant was increased from 65.44% (89/136) to 81.61% (111/136) on HRUS. Moreover, HRUS was effective in identifying a manufacturer of the device. CONCLUSIONS: In conclusion, our results indicate that HRUS is feasible in characterizing a breast implant in patients receiving an implant-based augmentation mammaplasty. But further prospective, large-scale studies are warranted to corroborate our results. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .


Assuntos
Implante Mamário , Implantes de Mama , Mamoplastia , Implante Mamário/efeitos adversos , Implante Mamário/métodos , Implantes de Mama/efeitos adversos , Estética , Feminino , Humanos , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Falha de Prótese , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia
14.
Eur J Cancer Care (Engl) ; 30(5): e13447, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33774893

RESUMO

OBJECTIVE: We investigated the contribution of supplement use to total nutrient intake, the prevalence of inadequate nutrient intake and the factors associated with supplement use among breast cancer survivors. METHODS: A total of 701 Korean breast cancer survivors were included. We calculated the contribution of dietary supplements to total nutrient intake and the proportion of the population below the estimated average requirements (EARs) or exceeding the tolerable upper intake levels (ULs). Stepwise logistic regression was used to identify factors associated with dietary supplement use. RESULTS: A total of 66.5% of the survivors used dietary supplements, with multivitamins and minerals being the most commonly consumed ones. The per cent contribution of supplement to the total intake was the highest for vitamin C. 28.2%-55.4% of the non-users consumed below the EAR of riboflavin, folate and calcium; 6.1%, 4.9% and 6.5% of the supplement users consumed above the UL of vitamins A and C, and iron, respectively. Supplement users had higher education levels or longer survival time. CONCLUSION: 66.5% of Korean breast cancer survivors used dietary supplements. A higher education level or prolonged survival time was associated with higher use of dietary supplements.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Estudos Transversais , Dieta , Suplementos Nutricionais , Ingestão de Alimentos , Feminino , Humanos , Sobreviventes
15.
Ann Surg Treat Res ; 100(3): 127-136, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33748026

RESUMO

PURPOSE: Papillary thyroid cancer (PTC) has a high incidence of BRAFV600E mutation. The purpose of this study was to evaluate the potential relationship between thyroiditis and BRAFV600E mutation status in patients with PTC. We investigated how a selective inhibitor of BRAFV600E PLX4032 affects the proliferation and inflammatory cytokine levels of thyroid cancer. METHODS: Two thyroid cancer cell lines TPC1 and 8505C were treated with PLX4032, an analysis was done on cell growth, cell cycle, the degree of apoptosis, and levels of inflammatory cytokines. To identify the functional links of BRAF, we used the STRING database. RESULTS: Docking results illustrated PLX4032 blocked the kinase activity by exclusively binding on the serine/threonine kinase domain. STRING results indicated BRAF is functionally linked to mitogen-activated protein kinase. Both cell lines showed a dose-dependent reduction in growth rate but had a different half maximal inhibitory concentration value for PLX4032. The reaction to PLX4032 was more sensitive in the 8505C cells than in the TPC1 cells. PLX4032 induced a G2/M phase arrest in the TPC1 cells and G0/G1 in the 8505C cells. PLX4032 induced apoptosis only in the 8505C cells. With PLX4032, the TPC1 cells showed decreased levels of vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein 1, whereas the 8505C cells showed significantly decreased levels of IL-8, serpin E1/plasminogen activator inhibitor-1, and matrix metalloproteinase (MMP)-3. CONCLUSION: PLX4032 was cytotoxic in both TPC1 and 8505C cells and induced apoptosis. In the 8505C cells, inflammatory cytokines such as IL-8 and MMP-3 were down-regulated. These findings suggest the possibility that the BRAFV600E mutation needs to target inflammatory signaling pathways in the treatment of thyroid cancer.

16.
Cancer Inform ; 19: 1176935120969696, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33223820

RESUMO

Prostaglandin-endoperoxide synthase-2 (PTGS2) plays a pivotal role in inflammation and carcinogenesis in human breast cancer. Our aim of the study is to find the prognostic value of PTGS2 in breast cancer. We conducted a multiomic analysis to determine whether PTGS2 functions as a prognostic biomarker in human breast cancer. We explored PTGS2 mRNA expressions using different public bioinformatics portals. Oncomine, Serial Analysis of Gene Expression (SAGE), GEPIA, ULCAN, PrognoScan database, Kaplan-Meier Plotter, bc-GenExMiner, USC XENA, and Cytoscape/STRING DB were used to identify the prognostic roles of PTGS2 in breast cancer. Based on the clinicopathological analysis, decreased PTGS2 expressions correlated positively with older age, lymph node status, the human epidermal growth factor receptor 2 (HER2) status (P < .0001), estrogen receptor (ER+) expression (P < .0001) Luminal A (P < .0001), and Luminal B (P < .0001). Interestingly, progesterone receptor (PR) (P < .0001) negative showed a high expression of PTGS2. Prostaglandin-endoperoxide synthase-2 was downregulated in breast cancer tissues than in normal tissues. In the PrognoScan database and, Kaplan-Meier Scanner, downregulated expressions of PTGS2 associated with poor overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival. The methylation levels were significantly higher in the Luminal B subtype. Through oncomine coexpressed gene analysis, we found a positive correlation between PTGS2 and interleukin-6 (IL-6) expression in breast cancer tissues. These results indicate that downregulated expressions of PTGS2 can be used as a promising prognostic biomarker and Luminal B hyper methylation may play an important role in the development of breast cancers. However, to clarify our results, extensive study is required.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33081213

RESUMO

Spousal support may attenuate stress in breast cancer survivors and improve their health-related quality of life (HRQoL). However, there is limited evidence of a relationship between spousal support, stress, and HRQoL in Asian populations. The current study examined whether spousal support, adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Survivors, and breastfeeding experience mediated or moderated the relationship between stress and HRQoL in Korean breast-cancer survivors. Between June 2016 and May 2018, 144 Korean women who survived breast cancer were recruited for the current cross-sectional study. Structured questionnaires and medical records were used to collect data. Structural equation modeling was used to examine mediating and moderating factors. Spousal support buffered the adverse effect of stress on HRQoL (ß= -0.22 for stress→spousal support; ß = 0.27 for spousal support→physical HRQoL; ß = 0.40 for spousal support→mental HRQoL). We found that adherence to ACS guidelines moderated the association between stress and HRQoL (ß = -0.14 for stress→mental HRQoL in high ACS adherence; ß = -0.79 for stress→mental HRQoL in low ACS adherence). Moreover, beta coefficients were -0.22 for stress→mental HRQoL in women with breastfeeding experience, and -0.71 in those without breastfeeding experience. In conclusion, spousal support mediated the association between stress and HRQoL and this association was moderated by both adherence to ACS guidelines and breastfeeding experience.


Assuntos
Aleitamento Materno , Neoplasias da Mama , Sobreviventes de Câncer , Exercício Físico , Qualidade de Vida , Estudos Transversais , Feminino , Humanos , Inquéritos e Questionários
18.
Sci Rep ; 10(1): 16792, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033299

RESUMO

Chronic shoulder pain is a common complication in breast cancer patients after surgery. Chronic shoulder pain after breast cancer surgery was formerly considered as neuropathic pain, however the pathophysiology including structural damages has not been assessed comprehensively. We hypothesized that the structural change could be one of the cause of shoulder pain after breast cancer surgery and evaluated various ultrasonography findings of the shoulder in breast cancer patients with chronic shoulder pain. Patients who were suffering from chronic shoulder pain on unilateral side for at least 3 months after breast cancer surgery were enrolled from a single tertiary hospital. Demographic and clinical data were collected at the baseline. Articular and adjacent structures of both shoulders (painful and contralateral side) were evaluated by ultrasonography. The ultrasonography findings were compared between painful and contralateral sides. Logistic regression analysis was performed to determine the factors associated with abnormal ultrasonography findings. Fifty-two female patients (average age of 55) were enrolled. Significantly more abnormal ultrasonography findings were observed in the painful side than in the contralateral side [39 (75.0%) vs 11 (21.2%), P < 0.001]. The coracohumeral ligament was significantly thicker in the painful side than in the contralateral side (2.48 ± 0.69 vs 1.54 ± 1.25 mm, P < 0.001); adhesive capsulitis was also more frequent in the painful side [14 (26.9%) vs 0, P < 0.001]. Furthermore, patients with a history of breast cancer surgery on the ipsilateral side were associated with abnormal ultrasonography findings and adhesive capsulitis. This study is the first to evaluate ultrasonography in patients with chronic shoulder pain after breast cancer surgery. The results showed that ultrasonography could reveal several structural problems in these patients.


Assuntos
Neoplasias da Mama/cirurgia , Dor Crônica/diagnóstico por imagem , Mastectomia/efeitos adversos , Dor de Ombro/diagnóstico por imagem , Dor Crônica/etiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Articulação do Ombro/diagnóstico por imagem , Dor de Ombro/etiologia , Ultrassonografia
19.
Breast ; 54: 121-126, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32980648

RESUMO

PURPOSE: Approval of eribulin for metastatic breast cancer was based on data primarily from Western patients, and there is a paucity of data on the effectiveness and safety of eribulin for Asian patients. To determine the effectiveness and safety of eribulin in Korean women with breast cancer in a real-world setting, we conducted a nationwide, multicenter, retrospective study. METHODS: Patients with locally advanced or metastatic breast cancer who were treated with eribulin in 14 centers throughout Korea were included in this study. Eribulin was generally administered at a dose of 1.23 mg/m2 (equivalent to 1.4 mg/m2 eribulin mesylate) by intravenous infusion for 2-5 min, or as a diluted solution, on Days 1 and 8 of every 21-day cycle. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included median PFS, overall survival (OS), time-to-treatment failure (TTF), tumor response rate, and incidence of hematologic treatment-emergent adverse events (TEAEs). RESULTS: The safety and full analysis populations included 398 and 360 (38 had no efficacy data) patients, respectively. The PFS rate at 6 months was 37.8%. Median PFS, OS, and TTF were 134, 631, and 120 days, respectively. Objective response rate, clinical benefit rate, and disease control rate were 18.1%, 50.6%, and 49.4%, respectively. Hematologic TEAEs were reported in 65.1% of patients; neutropenia (56.8%) and anemia (11.3%) were most common. CONCLUSION: Real-world effectiveness and safety of eribulin in Korean breast cancer patients were consistent with previous reports; no new safety concerns were identified.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento
20.
J Breast Cancer ; 23(3): 303-313, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32595992

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs). METHODS: Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs. RESULTS: At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased. The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower. CONCLUSION: This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.

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