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1.
Medicine (Baltimore) ; 98(43): e17746, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651908

RESUMO

As research progressed, the recommended duration of endocrine therapy for breast cancer patients has been extended from 5 to 10 years. This study aimed to investigate how the duration of endocrine medication and therapy affect survival rate in the real world. By using the National Health Insurance Research Database (NHIRD), this study examined 1002 breast cancer patients newly diagnosed between 2000 and 2005 as research subjects, and conducted follow-up until 2013. Among these subjects, 51 used aromatase inhibitors (AIs), 561 used tamoxifen, and 390 alternated between the use of tamoxifen and AIs. The mean follow-up period in this study was 9.63 years, and the mean duration of taking endocrine medication was 4.04 years. The tamoxifen group had the longest follow-up period (9.87 years), shortest endocrine therapy duration (3.29 years), and best survival rate (86.1%). Patients were divided into 3 groups based on the duration of endocrine therapy: under 2 years, 2 to 5 years, and over 5 years. It was found that patients who received medication for less than 2 years showed the lowest survival rate with statistically significant differences (P < .001). Therefore, the extension of endocrine therapy duration is critical in improving breast cancer patients' survival rate.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan
2.
Cancer Treat Rev ; 79: 101888, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491663

RESUMO

Metaplastic breast carcinomas (MPBC) are rare, aggressive and relatively chemorefractory tumors with a high unmet need. While most are "triple negative" and lack expression of estrogen, progesterone and HER2 receptors, MPBC are associated with worse outcomes compared to conventional triple negative invasive tumors. MPBCs are genetically heterogeneous and harbor somatic mutations, most frequently in TP53, PIK3CA and PTEN, with emerging studies suggesting a role for novel targeted therapies. These tumors have also been associated with overexpression of PD-L1 and tumor-infiltrating lymphocytes suggesting an endogenous immune response and therefore a rationale for treatment with immunotherapies. Here, we focus on therapeutic options for this difficult to treat breast cancer subtype and encourage physicians to consider targeted therapies/immunotherapies as part of ongoing clinical trials.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Animais , Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/mortalidade , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Gerenciamento Clínico , Transição Epitelial-Mesenquimal , Feminino , Variação Genética , Humanos , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(36): e16937, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490377

RESUMO

Metadherin (MTDH), also known as astrocyte elevated gene-1 (AEG-1), is an oncoprotein closely related to the development of breast cancer. However, few studies have been done on the expression and clinical significance of MTDH in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients.This study aimed to investigate the expression of MTDH in locally advanced HER-2 positive breast cancer, and evaluate the clinical significance of MTDH in predicting the prognosis of patients with HER-2 positive advanced breast cancer who received the neoadjuvant chemotherapy plus trastuzumab.In 144 HER-2 positive breast cancer tissues, 79 cases showed high expression of MTDH and 65 cases showed low expression. The expression of MTDH in locally advanced HER-2 positive breast cancer tissues was correlated with TNM stage, lymph node metastasis, Miller-Payne (MP) grade, and pathologic complete response (pCR) status (P < .05), but was not correlated with patient age, estrogen receptor (ER) expression level, progesterone receptor (PR) expression level, and Ki-67 expression level (P > .05). Kaplan-Meier univariate analysis revealed a negative correlation between MTDH expression and the disease-free survival (DFS) and overall survival (OS) in the post-operative patients with locally advanced HER-2 positive breast cancer (log rank test: P < .001). By using the COX proportional hazard regression model, it was found that MTDH expression, TNM stage, lymph node metastasis, and Ki-67 expression were closely related to DFS in patients. The hazard ratio (HR) of high MTDH expression was 1.816 (95% CI: 1.165-2.829). In addition, MTDH expression, TNM stage, and lymph node metastasis were also closely related to the OS of patient. The HR of the high expression of MTDH was 2.512 (95% CI: 1.472-4.286). The expression of MTDH in tumor tissues of patients with HER2-positive locally advanced breast cancer was significantly elevated, which was related to the poor pathological features.High MTDH expression was closely correlated with poor prognosis of patients and was an important factor affecting tumor progression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/biossíntese , Receptor ErbB-2/biossíntese , Trastuzumab/uso terapêutico , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/biossíntese
4.
Br J Radiol ; 92(1103): 20181026, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31529985

RESUMO

OBJECTIVE: To evaluate safety and efficacy of image guided-hypofractionated radiation therapy (IG-HRT) in patients with thoracic nodes oligometastases. METHODS: The present study is a multicenter analysis. Oligometastatic patients, affected by a maximum of five active lesions in three or less different organs, treated with IG-HRT to thoracic nodes metastases between 2012 and 2017 were included in the analysis. Primary end point was local control (LC), secondary end points were overall survival (OS), progression-free survival, acute and late toxicity. Univariate and multivariate analysis were performed to identify possible prognostic factors for the survival end points. RESULTS: 76 patients were included in the analysis. Different RT dose and fractionation schedules were prescribed according to site, number, size of the lymph node(s) and to respect dose constraints for relevant organs at risk. Median biologically effective dose delivered was 75 Gy (interquartile range: 59-86 Gy). Treatment was optimal; one G1 acute toxicity and seven G1 late toxicities of any grade were recorded. Median follow-up time was 23.16 months. 16 patients (21.05%) had a local progression, while 52 patients progressed in distant sites (68.42 %).Median local relapse free survival was not reached, LC at 6, 12 and 24 months was 96.05% [confidence interval (CI) 88.26-98.71%], 86.68% (CI 75.86-92.87) and 68.21% (CI 51.89-80.00%), respectively. Median OS was 28.3 months (interquartile range 16.1-47.2). Median progression-freesurvival was 9.2 months (interquartile range 4.1-17.93).At multivariate analysis, RT dose, colorectal histology, systemic therapies were correlated with LC. Performance status and the presence of metastatic sites other than the thoracic nodes were correlated with OS. Local response was a predictor of OS. CONCLUSION: IG-HRT for thoracic nodes was safe and feasible. Higher RT doses were correlated to better LC and should be taken in consideration at least in patients with isolated nodal metastases and colorectal histology. ADVANCES IN KNOWLEDGE: Radiotherapy is safe and effective treatment for thoracic nodes metastases, higher radiotherapy doses are correlated to better LC. Oligometastatic patients can receive IG-HRT also for thoracic nodes metastases.


Assuntos
Neoplasias do Mediastino/radioterapia , Neoplasias Torácicas/radioterapia , Idoso , Neoplasias da Mama/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Neoplasias Renais/mortalidade , Neoplasias Pulmonares/mortalidade , Metástase Linfática , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/mortalidade , Pessoa de Meia-Idade , Hipofracionamento da Dose de Radiação , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos , Neoplasias Torácicas/diagnóstico por imagem , Neoplasias Torácicas/mortalidade , Tomografia Computadorizada por Raios X/métodos
5.
Gene ; 721: 144100, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31493508

RESUMO

BACKGROUND: Breast cancer (BRCA) is the most prevalent cancer that threatens female health. A growing body of evidence has demonstrated the non-negligible effects of messenger RNAs (mRNAs) on biological processes involved in cancers; however, there is no definite conclusion regarding the role of mRNAs in predicting the prognosis of BRCA patients. MATERIALS AND METHODS: We systematically screened the mRNA expression landscape and clinical data of samples from the Cancer Genome Atlas (TCGA). Univariate Cox analysis and robust likelihood-based survival analysis were conducted to identify key mRNAs associated with BRCA. Furthermore, risk scores based on multivariate Cox analysis divided the training set into high-risk and low-risk groups. ROC analysis determined the optimal cut-off point for patient classification of risk levels. The prognostic model was additionally validated in the testing set and complete dataset. Finally, we plotted the survival curves for the mRNAs used in our model. RESULTS: We obtained the original expression data of 13,617 mRNAs from a total of 1088 samples. After comprehensive survival analysis, the four-mRNA (ACSL1, OTUD3, PKD1L2, and WISP1) prognosis risk assessment model was constructed. Furthermore, the area under cure (AUC) was 0.834, indicating that the model was meaningful and reasonable. In each dataset, analysis based on the four-mRNA signature risk score indicated that the survival status of the group with high risk score was worse than that of the group with low risk scores. Patients with strong mRNA expression of OTUD3, PKD1L2, and WISP1 tended to have good prognosis, whereas patients with high ACSL1 expression tended to have poor prognosis. CONCLUSION: In summary, we constructed a four-mRNA prognosis risk assessment model for BRCA. The newly developed model offers more possibilities for assessing prognosis and guiding the selection of better treatment strategies for BRCA.


Assuntos
Neoplasias da Mama , Bases de Dados de Ácidos Nucleicos , Modelos Biológicos , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Proteínas de Sinalização Intercelular CCN/biossíntese , Proteínas de Sinalização Intercelular CCN/genética , Coenzima A Ligases/biossíntese , Coenzima A Ligases/genética , Intervalo Livre de Doença , Feminino , Humanos , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptores Acoplados a Proteínas-G/biossíntese , Receptores Acoplados a Proteínas-G/genética , Taxa de Sobrevida , Proteases Específicas de Ubiquitina/biossíntese , Proteases Específicas de Ubiquitina/genética
6.
Zhonghua Zhong Liu Za Zhi ; 41(9): 681-685, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550858

RESUMO

Objective: To investigate the expression discordances of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor2 (HER-2) and Ki-67 in primary and metastatic breast cancer specimens and explore the clinical significances. Methods: Biopsies of metastatic lesions were performed in 203 patients with breast cancer recurrence and metastasis indicated by physical examination and/or imaging examination. We confirmed pathological properties and assessed the expressions of ER, PR, HER-2 and Ki-67 in primary and metastatic lesions, their relationships with prognosis were also analyzed. Results: Biopsy failed in 3 patients, the pathology and immunohistochemitry results of metastatic lesions were not obtained. One person was diagnosed as tuberculosis and another was primary lung cancer. Among the 198 cases of primary and metastatic lesions, the discordance rates of ER, PR, HER-2 and Ki-67 were 27.3%, 34.3%, 11.8% and 15.1%, respectively.The expressions of ER, HER-2 and Ki-67 were not significantly different between the primary and metastatic lesions, however, the expressions of PR were more likely to turn negative in the metastases (P<0.001). The disease-free survival (DFS) of patients with ER, PR positive, HER-2 negative and low expression of Ki-67 in metastatic lesion was much longer (P<0.05). Conclusions: The expressions of ER, PR, HER-2 and Ki-67 in metastatic lesions are associated with the prognosis of breast cancer patients.Their expression discordances between primary and metastatic lesions can guide the treatment and evaluate the risks of recurrence and prognosis.


Assuntos
Neoplasias da Mama/metabolismo , Antígeno Ki-67/metabolismo , Recidiva Local de Neoplasia/metabolismo , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Biópsia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida
7.
Zhonghua Zhong Liu Za Zhi ; 41(9): 686-692, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550859

RESUMO

Objective: To analyze the clinicopathological features and prognosis of breast invasive ductal carcinoma patients receiving radical mastectomy according to the primary tumor location. Methods: From January 2008 to December 2008, 993 patients with breast invasive ductal carcinoma received radical mastectomy in Tianjin Medical University Cancer Institute and Hospital. Patients were grouped according to the primary tumor location when breast cancer was diagnosed. The clinicopathological characteristics and follow-up information of them was collected and analyzed retrospectively. Results: Of the 993 patients, primary tumor located in the upper-outer quadrant (UOQ) in 556 patients (56.0%), the lower-outer quadrant (LOQ) in 97 (9.8%), the central portion in 99 (10.0%), the upper-inner quadrant (UIQ) in 186 (18.7%), and the lower-inner quadrant (LIQ) in 55 (5.5%). Patients in the central portion tended to have larger tumors, and more patients in the upper-inner quadrant received endocrine therapy. The estimated 5-year disease-free survival (DFS) rates of patients with primary lesion in the UOQ, LOQ, central portion, UIQ and LIQ were 90.3%, 88.7%, 79.8%, 86.0% and 72.7%, respectively, with significant differences (P<0.001). The 5-year overall survival (OS) rates were 97.5%, 96.9%, 90.9%, 94.1% and 87.3%, respectively, with significant differences (P<0.001). Multivariate analysis showed that 5-year recurrence and metastasis risks were significantly increased in patients with primary lesion in the central portion, UIQ and LIQ compared to other groups (P<0.001), and 5-year mortality risks were increased in these three groups (P=0.002). Conclusion: Primary lesion located in central portion and inner quadrant is an independent adverse prognostic factor for patients with breast invasive ductal carcinoma patients receiving radical mastectomy.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Mastectomia , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/cirurgia , Humanos , Linfonodos , Metástase Linfática/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
8.
Anticancer Res ; 39(9): 5009-5018, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519608

RESUMO

BACKGROUND/AIM: Interleukin (IL)-18, which belongs to the IL-1 superfamily of cytokines, is a known interferon-gamma (IFN-γ)-inducing factor. Since IFN-γ plays an essential role in anticancer immunity mediated through cytotoxic T cells, IL-18 may also contribute to the function of immunosurveillance. The aim of the study was to examine the association of IL-18 with the outcomes of patients with breast cancer. PATIENTS AND METHODS: Serum IL-18 levels were determined at baseline in 270 patients operated for breast cancer, and the relapse-free survival (RFS) was compared between IL-18-high and -low groups. The relationships between IL-18 and tumor-infiltrating lymphocytes (TILs) or the neutrophil-to-lymphocyte ratio (NLR) were also investigated. RESULTS: The RFS of patients was significantly better in the IL-18-low group than in the IL-18-high group (p=0.032). According to the multivariate analysis, IL-18 was a significant and independent predictive factor for RFS (hazard ratio(HR)=0.336; 95% confidence interval(CI)=0.147-0.727; p=0.0053). No association was observed between the IL-18 levels and TILs or NLRs. CONCLUSION: IL-18 levels may be useful for predicting the prognosis of patients who have received surgical treatment for breast cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Interleucina-18/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neutrófilos/imunologia , Neutrófilos/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Valores de Referência , Estudos Retrospectivos , Carga Tumoral
9.
Anticancer Res ; 39(9): 5135-5142, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519625

RESUMO

AIM: To compare the overall survival (OS) of patients with locoregional and metastatic breast cancer (BC) considering baseline demographic, clinical and contextual characteristics. MATERIALS AND METHODS: A retrospective analysis of a cancer registry was conducted, using the Kaplan-Meier and Mantel-Cox analyses for the calculation of median OS and cumulative survival. RESULTS: The median OS was 112 months, being longer in patients with locoregional versus those with metastatic BC at diagnosis (115 vs. 31 months, p<0.001). The cumulative survival at 1, 3 and 5 years were 94.9%, 85.6% and 76.5%, respectively. More recent year of diagnosis [hazard ratio (HR)=1.09] and age at diagnosis (≥65 vs. 40 years, HR=2.79) and presence of metastatic disease (HR=5.69) were associated with a shorter OS. The region of residence, morphology and topography of the tumor were also associated with survival in patients with BC. Rurality was only associated with lower survival in patients with metastatic BC. CONCLUSION: This study identified significant differences in the median OS of patients with locoregional and those with metastatic BC considering their baseline characteristics.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
10.
Cancer Sci ; 110(10): 3368-3374, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432574

RESUMO

BRCA1/2 genes are the most frequently germline mutated DNA-repair genes, and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non-BRCA1/2 DNA-repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA-repair genes were determined using a multigene panel in 7657 BRCA1/2-negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2-negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 DNA-repair genes. The prevalence of DNA-repair gene mutations was significantly higher in familial breast cancers (5.2%, P = 0.002) and early-onset breast cancers (diagnosed at and before the age of 40) (4.5%, P = 0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA-repair gene mutation carriers were significantly more likely to have a larger tumor (P = 0.04) and axillary lymph node metastasis (P = 0.03). Moreover, DNA-repair gene mutation was an independent unfavorable factor for recurrence-free survival (adjusted hazard ratio [HR] = 1.38, 95% CI: 1.00-1.91, P = 0.05) and disease-specific survival (adjusted HR=1.63, 95% CI: 1.04-2.57, P = 0.03) in this cohort. Overall, 3.4% of BRCA1/2-negative breast cancer patients carried germline mutations in the 16 DNA-repair genes, and the DNA-repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.


Assuntos
Neoplasias da Mama/patologia , Reparo do DNA , Mutação em Linhagem Germinativa , Metástase Linfática/patologia , Análise de Sequência de DNA/métodos , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Predisposição Genética para Doença , Humanos , Metástase Linfática/genética , Pessoa de Meia-Idade , Análise de Sobrevida , Carga Tumoral , Adulto Jovem
11.
Medicine (Baltimore) ; 98(31): e16625, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374029

RESUMO

Cullin proteins couple with RING-finger proteins, adaptor proteins and substrate recognition receptors to form E3 ubiquitin ligases for recognizing numerous substrates and participating in a variety of cellular processes, especially in genome stability and tumorigenesis. However, the prognostic values of Cullins in breast cancer remain elusive.A "Kaplan-Meier plotter" (KM plotter) online survival analysis tool was used to evaluate the association of individual Cullin members' mRNA expression with overall survival (OS) in breast cancer patients.Our results revealed that elevated mRNA expression of CUL4A and PARC were significantly associated with poor OS for breast cancer patients. While high mRNA expression of CUL2, CUL4B, and CUL5 were correlated with better survival for breast cancers.The associated results suggested that some Cullin members could serve as new predictive prognostic indicators for breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Proteínas Culina/biossíntese , RNA Mensageiro/biossíntese , Neoplasias da Mama/patologia , Proteínas de Transporte/biossíntese , Humanos , Estimativa de Kaplan-Meier , Gradação de Tumores
12.
DNA Cell Biol ; 38(10): 1088-1099, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31424267

RESUMO

The biological functions of lipocalin-1 (LCN1) are involved in innate immune responses and act as a physiological scavenger of potentially harmful lipophilic molecules. However, the relevance of LCN1 with cancer is rarely concerned currently. The aim of this study is to address the relevance of LCN1 with BRCA by bioinformatics. In this study, we found that the expressions of LCN1 increased significantly in various cancerous tissues, including BRCA, compared with their adjacent normal tissues through the TIMER database. Furthermore, UALCAN database analysis showed that the expression of LCN1 increased gradually from stage 1 to stage 4 and was upregulated in BRCA patients with different races and subtypes compared with that in the normal. In addition, those patients with perimenopause and postmenopause status displayed higher LCN1 expression. Importantly, LCN1 genetic alterations, including copy number amplification, deep deletion, and missense mutation, could be found, and the alteration frequency showed difference in various invasive BRCA through cBioPortal database. Moreover, a positive correlation between LCN1 somatic copy number alterations and immune cell enrichments was revealed in basal like BRCA by GISTIC 2.0. Finally, analysis on prognostic value of LCN1 by Kaplan-Meier plotter showed that low LCN1 expression correlated with poor prognosis for relapse-free survival in all types of BRCA, overall survival in luminal B BRCA, distant metastasis free survival in human epithelial growth factor receptor-2 (HER2) positive BRCA, and postprogression survival (PPS) in luminal A BRCA. But high LCN1 expression also displayed poor prognosis for PPS in HER2 positive BRCA. The results together verified the significance of LCN1 in BRCA, suggesting that it may be a potential biomarker for BRCA diagnosis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Lipocalina 1/genética , Recidiva Local de Neoplasia/genética , Receptor ErbB-2/genética , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Feminino , Humanos , Lipocalina 1/imunologia , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Perimenopausa/genética , Pós-Menopausa/genética , Pós-Menopausa/imunologia , Receptor ErbB-2/imunologia , Análise de Sobrevida
13.
Medicine (Baltimore) ; 98(33): e16773, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415379

RESUMO

Conventional therapy modalities for advanced breast cancer are problematic, whereas checkpoint blockade immunotherapy has been considered as a promising approach. This study aims to determine programmed death-ligand 1 (PD-L1) expression and methylation status of PD-L1 promoter in primary tumor tissue and metastatic foci of patients with stage IV breast cancer.Clinicopathological data and survival rates of 57 breast cancer patients, who were initially staged IV, and operated for intact tumors, were retrospectively analyzed. Immunohistochemical analysis of PD-L1 using 57 primary tumors, 33 paired metastatic lymph nodes, and 14 paired distant metastases was performed. Additionally, the methylation rate of the PD-L1 gene promoter region was determined with real-time polymerase chain reaction (PCR) analysis in 38 samples.Overall PD-L1 expression in primary tumors was 23.1% (12/52). PD-L1 positivity was reduced in lymph nodes by 15.2% (5/33) and in distant metastases by 21.4% (3/14). PD-L1 expression diverged between primary and metastatic foci in a subset of cases (18.2% for lymph node and 33.3% for distant metastasis). In general, the PD-L1 promoter was not methylated, and mean methylation rates were low (min. 0%-max. 21%). We observed no correlation between PD-L1 expression, promoter methylation, and survival.Neither the expression nor the methylation status of PD-L1 in patients, who were presented with stage IV breast cancer and operated for an intact primary tumor, had a statistically significant relation with survival. Discordance in PD-L1 expression between primary tumor and metastasis should be considered during pathological and clinical management of patients who would undergo checkpoint blockade therapy.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias da Mama/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metilação , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Receptor de Morte Celular Programada 1/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Turquia
14.
J Cancer Res Clin Oncol ; 145(9): 2383-2396, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280346

RESUMO

PURPOSE: Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. Weighted gene co-expression network analysis was used to construct free-scale gene co-expression networks and to identify potential biomarkers for breast cancer progression. METHODS: The gene expression profiles of GSE42568 were downloaded from the Gene Expression Omnibus database. RNA-sequencing data and clinical information of breast cancer from TCGA were used for validation. RESULTS: A total of ten modules were established by the average linkage hierarchical clustering. We identified 58 network hub genes in the significant module (R2 = 0.44) and 6 hub genes (AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK), which were significantly correlated with prognosis. Receiver-operating characteristic curve validated that the mRNA levels of these six genes exhibited excellent diagnostic efficiency in the test data set of GSE42568. RNA-sequencing data from TCGA showed that the expression levels of these six genes were higher in triple-negative tumors. One-way ANOVA suggested that these six genes were upregulated at more advanced stages. The results of independent sample t test indicated that MCM10 and TTK were associated with tumor size, and that AGO2, CDC20, CDCA5, MCM10, and MYBL2 were overexpressed in lymph-node positive breast cancer. CONCLUSIONS: AGO2, CDC20, CDCA5, MCM10, MYBL2, and TTK were identified as candidate biomarkers for further basic and clinical research on breast cancer based on co-expression analysis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Redes Reguladoras de Genes , Transcriptoma , Biomarcadores Tumorais/análise , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Análise por Conglomerados , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Ensaios de Triagem em Larga Escala , Humanos , Análise em Microsséries , Prognóstico
15.
Am Surg ; 85(6): 645-653, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31267907

RESUMO

The purpose of this meta-analysis was to determine the value of quantitative dynamic contrast-enhanced (DCE) MRI (DCE-MRI) in evaluating the response of breast cancer to neoadjuvant chemotherapy (NAC). PubMed, Embase, and Cochrane Library databases (from building to July 31, 2018) were searched to collect articles about the therapeutic evaluation of NAC using the quantitative DCE-MRI in patients with breast cancer. The sensitivities and specificities of quantitative DCE-MRI in the evaluation of NAC for breast cancer were extracted from the articles. Meta-DiSc1.4 was applied to evaluate the efficacy of the sensitivity and specificity; forest figure and summary receiver operating characteristics (SROC) were created. A total of 356 articles were enrolled in this study, including 739 cases in total, in which 218 cases were effective and the other 521 cases were ineffective to NAC, considering the pathological results as the gold standard. The sensitivity and specificity in the included 14 articles of quantitative DCE-MRI (Ktrans, Kep, and ve) in comprehensively evaluating NAC for breast cancer were 84 per cent (95% confidence interval (CI): 78-88%) and 83 per cent (95% CI: 79-86%), respectively. The area under SROC was 0.899 (95% CI: 0.867-0.943). The sensitivity and specificity in the three articles of Ktrans evaluating NAC for breast cancer were 84.1 per cent (95% CI: 71.0-92.1%) and 81.3 per cent (95% CI: 70.5%-88.5%), respectively. The area under SROC was 0.899 (95% CI: 0.834-0.962). Our study confirmed that the quantitative DCE-MRI is able to monitor NAC treatment for breast cancer because of its high sensitivity and specificity. However, there is a high degree of heterogeneity in published studies, highlighting the lack of standardization in the field.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Meios de Contraste , Imagem por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Intensificação de Imagem Radiográfica/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Neoplasias da Mama/mortalidade , Estudos de Avaliação como Assunto , Medicina Baseada em Evidências , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Medição de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do Tratamento
16.
Nuklearmedizin ; 58(3): 242-248, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31167272

RESUMO

AIM: To evaluate the feasibility of early metabolic response assessment with 18F-FDG PET/CT in patients with breast cancer liver metastases 4 weeks after radioembolization with Yttrium-90 labeled microspheres. METHODS: 25 patients (mean age 58y, range 40-74) with advanced stage liver metastases of breast cancer were treated with 1.9 ± 0.4 GBq of 90Y-microspheres in the salvage setting and underwent 18F-FDG PET/CT at baseline and 4 weeks post-radioembolization. 14 patients (56 %) had an excessive hepatic tumor burden (> 50 % of total liver volume), 21 patients (84 %) had extrahepatic disease. Liver lesions with the highest SUVmax were selected as target lesions and a cut-off was set at 50 % reduction to separate responders from non-responders. The predictive impact of metabolic response on overall survival (OS) was investigated along with other prognostic factors. RESULTS: The median OS in this highly advanced metastatic cohort was 7 months (95 % CI, 5-9). All patients had a reduction in SUVmax (mean ΔSUVmax: -49 ± 26 %) at 4 weeks post-treatment. Patients with > 50 % SUVmax reduction survived longer (median OS 13 mo, 95 % CI 8-18) than the remaining patients (median OS 4 mo, 95 % CI 2-6; p = 0.001). From all investigated baseline factors including age, performance status, and presence of extra-hepatic disease, only the hepatic tumor burden had a significant impact on OS (p = 0.02). CONCLUSIONS: This is the first preliminary evidence in breast cancer that early post-radioembolization molecular response assessment of treated liver metastases - as early as 4 weeks posttreatment - may predict survival. If confirmed by larger series, FDG PET/CT could be considered for early response-adapted treatment modifications.


Assuntos
Neoplasias da Mama/mortalidade , Fluordesoxiglucose F18/uso terapêutico , Neoplasias Hepáticas/mortalidade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Braquiterapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Microesferas , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Radioisótopos de Ítrio/química
17.
J Surg Oncol ; 120(2): 148-159, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172534

RESUMO

BACKGROUND: Adherence to evidence-based standards can lead to improved outcomes for patients with breast cancer. However, adherence rates to standards and their effects on patient outcomes are unknown. OBJECTIVES: To examine adherence rates to standards compiled by the American College of Surgeons Clinical Research Program and its effects on patient outcomes. METHODS: Using the National Cancer Database (2004-2015), we identified cohorts of breast cancer patients: clinical T1N0M0 under age of 70 (cT1), clinical T2N0M0 or T3N0M0 (cT2/3), and clinical M0 and pathologic N2 or N3 (pN2/3). Standards included negative margins, any adjuvant therapy, and two or more lymph nodes (LNs) examined (for cT1 or cT2/3 patients) or more than 10 LNs examined (for pN2/3 patients). We performed Kaplan-Meier and Cox proportional hazards analysis. RESULTS: We identified 318 853 (65.0%) cT1, 164 593 (67.3%) cT2/3, and 77 626 (67.7%) pN2/3 patients who met the standards. More than 90% of patients had negative margins and adjuvant therapy, but less than 80% met LN standards. The median overall survival (OS) was significantly longer for patients who met the standards. Individual components of the standards were predictors of improved OS. CONCLUSIONS: One-third of patients did not meet the evidence-based standards in their treatment for breast cancer. Efforts to improve the knowledge of and adherence to these standards should be emphasized.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Fidelidade a Diretrizes , Idoso , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Margens de Excisão , Mastectomia , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Modelos de Riscos Proporcionais
18.
BMC Public Health ; 19(1): 823, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242882

RESUMO

BACKGROUND: Triggered by the successive implementation of organized mammography screening programs (MSPs) throughout western European countries over the last decades, there is an ongoing debate questioning their effectiveness. Since it is difficult to assess the effect of MSPs on a population level, we rather aim to assess the impact of the implementation itself on breast cancer mortality rates utilizing an ecological study design. METHODS: We analyzed age group-specific (50-59, 60-69 and 70-79 years) female breast cancer mortality rates in 14 western European countries between 1980 and 2017 using Joinpoint regression, interrupted time series (ITS) regression and multivariable Poisson regression. RESULTS: The Joinpoint analysis demonstrated decreasing trends resulting in annual percentage changes ranging from - 1.5% to - 5.4% (50-59), - 0.2% to - 8.1% (60-69) and 0% to - 7.1% (70-79) depending on the country within 3 years after MSP implementation. The ITS analysis results in highly significant interaction terms (calendar year * binary MSP indicator) for all age groups. The multivariable regression using "calendar year", "year of MSP implementation" and "years with MSP" as independent variables yielded a significant yearly decrease for "years with MSP" ranging from 0.9 to 1.2%. CONCLUSIONS: The results of this study suggest a positive association between the implementation of MSPs and the (accelerated) reduction of breast cancer mortality rates. Measuring and quantifying the isolated effect of MSPs on a population level will require additional studies using individual data.


Assuntos
Neoplasias da Mama/mortalidade , Detecção Precoce de Câncer/métodos , Mamografia , Programas de Rastreamento , Avaliação de Programas e Projetos de Saúde , Idoso , Neoplasias da Mama/etnologia , Causas de Morte , Europa (Continente)/epidemiologia , Feminino , Programas Governamentais , Humanos , Análise de Séries Temporais Interrompida , Mamografia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Resultado do Tratamento
19.
N Engl J Med ; 381(4): 307-316, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31166679

RESUMO

BACKGROUND: An earlier analysis of this phase 3 trial showed that the addition of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor to endocrine therapy provided a greater benefit with regard to progression-free survival than endocrine therapy alone in premenopausal or perimenopausal patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here we report the results of a protocol-specified interim analysis of the key secondary end point of overall survival. METHODS: We randomly assigned patients to receive either ribociclib or placebo in addition to endocrine therapy (goserelin and either a nonsteroidal aromatase inhibitor or tamoxifen). Overall survival was evaluated with the use of a stratified log-rank test and summarized with the use of Kaplan-Meier methods. RESULTS: A total of 672 patients were included in the intention-to-treat population. There were 83 deaths among 335 patients (24.8%) in the ribociclib group and 109 deaths among 337 patients (32.3%) in the placebo group. The addition of ribociclib to endocrine therapy resulted in significantly longer overall survival than endocrine therapy alone. The estimated overall survival at 42 months was 70.2% (95% confidence interval [CI], 63.5 to 76.0) in the ribociclib group and 46.0% (95% CI, 32.0 to 58.9) in the placebo group (hazard ratio for death, 0.71; 95% CI, 0.54 to 0.95; P = 0.00973 by log-rank test). The survival benefit seen in the subgroup of 495 patients who received an aromatase inhibitor was consistent with that in the overall intention-to-treat population (hazard ratio for death, 0.70; 95% CI, 0.50 to 0.98). The percentage of patients who received subsequent antineoplastic therapy was balanced between the groups (68.9% in the ribociclib group and 73.2% in the placebo group). The time from randomization to disease progression during receipt of second-line therapy or to death was also longer in the ribociclib group than in the placebo group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.55 to 0.87). CONCLUSIONS: This trial showed significantly longer overall survival with a CDK4/6 inhibitor plus endocrine therapy than with endocrine therapy alone among patients with advanced hormone-receptor-positive, HER2-negative breast cancer. No new concerns regarding toxic effects emerged with longer follow-up. (Funded by Novartis; MONALEESA-7 ClinicalTrials.gov number, NCT02278120.).


Assuntos
Aminopiridinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Inibidores de Proteínas Quinases/administração & dosagem , Purinas/administração & dosagem , Adulto , Aminopiridinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Pessoa de Meia-Idade , Perimenopausa , Pré-Menopausa , Inibidores de Proteínas Quinases/efeitos adversos , Purinas/efeitos adversos , Receptor ErbB-2 , Receptores Estrogênicos , Receptores de Progesterona , Análise de Sobrevida , Tamoxifeno/administração & dosagem
20.
BMC Health Serv Res ; 19(1): 387, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200700

RESUMO

BACKGROUND: Australia's Aboriginal and Torres Strait Islander women have poorer survival and twice the disease burden from breast cancer compared to other Australian women. These disparities are influenced, but not fully explained, by more diagnoses at later stages. Incorporating breast screening, hospital and out of hospital treatment and cancer registry records into a person-linked data system can improve our understanding of breast cancer outcomes. We focussed one such system on a population-based cohort of Aboriginal women in South Australia diagnosed with breast cancer and a matched cohort of non-Aboriginal women with breast cancer. We quantify Aboriginal and non-Aboriginal women's contact with publicly funded screening mammograms; quantify exposure to a selection of cancer treatment modalities; then assess the relationship between screening, treatment and the subsequent risk of breast cancer death. METHODS: Breast cancers registered among Aboriginal women in South Australia in 1990-2010 (N = 77) were matched with a random selection of non-Aboriginal women by birth and diagnostic year, then linked to screening records, and treatment 2 months before and 13 months after diagnosis. Competing risk regression summarised associations of Aboriginality, breast screening, cancer stage and treatment with risk of breast cancer death. RESULTS: Aboriginal women were less likely to have breast screening (OR = 0.37, 95%CIs 0.19-0.73); systemic therapies (OR = 0.49, 95%CIs 0.24-0.97); and, surgical intervention (OR = 0.35, 95%CIs 0.15-0.83). Where surgery occurred, mastectomy was more common among Aboriginal women (OR = 2.58, 1.22-5.46). Each of these factors influenced the risk of cancer death, reported as sub-hazard ratios (SHR). Regional spread disease (SHR = 34.23 95%CIs 6.76-13.40) and distant spread (SHR = 49.67 95%CIs 6.79-363.51) carried more risk than localised disease (Reference SHR = 1). Breast screening reduced the risk (SHR = 0.07 95%CIs 0.01-0.83). So too did receipt of systemic therapy (SHR = 0.06 95%CIs 0.01-0.41) and surgical treatments (SHR = 0.17 95%CIs 0.04-0.74). In the presence of adjustment for these factors, Aboriginality did not further explain the risk of breast cancer death. CONCLUSION: Under-exposure to screening and treatment of Aboriginal women with breast cancers in South Australia contributed to excess cancer deaths. Improved access, utilisation and quality of effective treatments is needed to improve survival after breast cancer diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico , Disparidades em Assistência à Saúde/etnologia , Adulto , Neoplasias da Mama/etnologia , Neoplasias da Mama/mortalidade , Estudos de Coortes , Detecção Precoce de Câncer/normas , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Serviços de Saúde do Indígena/normas , Serviços de Saúde do Indígena/estatística & dados numéricos , Humanos , Mamografia/estatística & dados numéricos , Mastectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Grupo com Ancestrais Oceânicos/etnologia , Sistema de Registros , Pesquisa , Estudos Retrospectivos , Austrália do Sul/etnologia
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