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1.
BMC Cancer ; 21(1): 434, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879104

RESUMO

BACKGROUND: Interactions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR-/HER2-). METHODS: A total of 735 patients with early-stage invasive BC (1999-2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model. RESULTS: Patients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). CONCLUSIONS: Adipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.


Assuntos
Tecido Adiposo/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Comunicação Celular , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/etiologia , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/terapia , Microambiente Tumoral
2.
N Engl J Med ; 384(16): 1529-1541, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33882206

RESUMO

BACKGROUND: Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker. METHODS: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases. RESULTS: A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment. CONCLUSIONS: Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Moléculas de Adesão Celular/antagonistas & inibidores , Imunoconjugados/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígenos de Neoplasias , Antineoplásicos/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoconjugados/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/mortalidade , Carga Tumoral
3.
BMC Cancer ; 21(1): 239, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676425

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1. METHODS: Immunohistochemical staining (primary antibodies of 73-10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined. RESULTS: Thirty-four (55.7%) patients were positive for CAF PD-L1 (73-10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73-10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044-0.891; p = 0.035). CONCLUSIONS: CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73-10 assay may be suitable for immunostaining CAF PD-L1.


Assuntos
Fibroblastos Associados a Câncer/imunologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias de Mama Triplo Negativas/mortalidade , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Antígeno B7-H1/metabolismo , Mama/imunologia , Mama/patologia , Mama/cirurgia , Fibroblastos Associados a Câncer/metabolismo , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
4.
BMC Cancer ; 21(1): 238, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676449

RESUMO

BACKGROUND: Liver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM). METHODS: Data on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients. RESULTS: Young age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001). CONCLUSIONS: Breast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/terapia , Quimiorradioterapia Adjuvante/métodos , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Prognóstico , Receptor ErbB-2/análise , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/análise , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/análise , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/terapia , Adulto Jovem
5.
BMC Cancer ; 21(1): 286, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726701

RESUMO

BACKGROUND: In this study, we investigated CD20+ TILs in triple-negative breast cancer (TNBC) and their relationship with T lymphocyte subsets (CD4+, CD8+, CD25+, and FOXP3+), including their combined prognostic value using an immunohistochemical staining method. METHODS: We investigated 107 patients with TNBC for whom a full-face section stained by hematoxylin and eosin between 2006 and 2018 at Dokkyo Medical University Hospital was available. RESULTS: The strongest association of infiltrating CD20+ TILs was with CD4+ TILs. There was a significant relationship between CD20+ and CD4+ TILs (r = 0.177; p < 0.001), CD8+ TILs (r = 0.085; p = 0.002), and FOXP3+ TILs (r = 0.0043; p = 0.032). No significant relationships were observed between the CD20+ and CD25+ TILs (r = 0.012; p = 0.264). Multivariate analysis revealed that only the CD20+/FOXP3 ratio was an independent factor for relapse-free survival (p < 0.001) and overall survival (p < 0.001). Patients with tumors highly infiltrated by CD4+, CD8+, and CD20+ TILs had a good prognosis. In contrast, those with tumors weakly infiltrated by CD20+ TILs but highly infiltrated by CD25+ and FOXP3+ TILs had a poor prognosis. CONCLUSIONS: CD20+ TILs may support an increase in CD4+ and CD8+ TILs, which altered the anti-tumor response, resulting in a positive prognosis. CD20+ TILs correlated with FOXP3+ Treg lymphocytes, which were reported to be correlated with a poor prognosis. Our study suggested that TIL-B cells have dual and conflicting roles in TIL-T immune reactions in TNBC.


Assuntos
Carcinoma/terapia , Linfócitos do Interstício Tumoral/imunologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias de Mama Triplo Negativas/terapia , Linfócitos B/imunologia , Mama/citologia , Mama/imunologia , Mama/patologia , Carcinoma/imunologia , Carcinoma/mortalidade , Carcinoma/patologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Medição de Risco/métodos , Subpopulações de Linfócitos T/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
6.
J Int Med Res ; 49(2): 300060521991019, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33541181

RESUMO

OBJECTIVE: Nearly 5% of patients with breast cancer carry germline BRCA mutations, which are more common in triple-negative breast cancer (TNBC). Previous clinical trials demonstrated the therapeutic efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) against BRCA-mutated metastatic breast cancer. The current study conducted a systemic review and meta-analysis of the clinical efficiency and safety of PARPis, either alone or combined with chemotherapy, in patients with TNBC. METHODS: We searched PubMed, EMBASE, and ClinicalTrials.gov to identify randomized controlled trials comparing PARPi therapy with chemotherapy, and comparisons of chemotherapy plus PARPis with chemotherapy alone were included. The study endpoints included the clinical response, progression-free survival, and adverse event rates. RESULTS: PARPi therapy was revealed to improve progression-free survival in patients with advanced breast cancer, either alone or in combination with chemotherapy. Subgroup analysis illustrated that patients with mutant BRCA1 and mutant BRCA2 and those who had not been treated with platinum-based agents could specifically benefit from PARPis. CONCLUSION: PARPi monotherapy can significantly improve clinical outcomes in patients with advanced breast cancer, especially those with TNBC, those who had not previously received platinum therapy, and those with mutant BRCA1/2. PARPis combined with chemotherapy represent new treatment options for patients with advanced cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Proteína BRCA1/genética , Proteína BRCA2/genética , Feminino , Humanos , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
7.
Clin Immunol ; 225: 108679, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33485895

RESUMO

HER2-targeted therapy has not benefited patients with low levels of HER2 expression; however, combination therapy may be effective. Primary analysis of a phase IIb trial investigating the HER2-derived vaccine nelipepimut-S (NPS) did not benefit the intention-to-treat population, but subset analysis showed a benefit in triple-negative breast cancer (TNBC) patients. The subset analysis of this multicenter, randomized, single-blind, phase IIb trial identified significant improvement in 36-month disease-free survival (DFS) between NPS (n = 55) and placebo (n = 44) in TNBC (HR 0.25, p = 0.01) and those who express HLA-A24 (HR 0.41, p = 0.05). The TNBC cohort demonstrated improved 36-month DFS in those with HER2 1+ expression (HR 0.17, p = 0.01), HLA-A24 positivity (HR 0.08, p < 0.01), or in those who received neoadjuvant chemotherapy (HR 0.21, p < 0.01). NPS vaccination with trastuzumab was associated with improved 36-month DFS among patients with TNBC. The observed benefit to this high-risk subgroup warrants confirmation in a phase III trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Imunoterapia/métodos , Fragmentos de Peptídeos/imunologia , Receptor ErbB-2/imunologia , Trastuzumab/uso terapêutico , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Antígeno HLA-A24/metabolismo , Humanos , Análise de Intenção de Tratamento , Recidiva Local de Neoplasia , Efeito Placebo , Medicina de Precisão , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Risco , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/mortalidade
8.
Am J Clin Oncol ; 44(3): 105-108, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481372

RESUMO

OBJECTIVE: Eribulin mesylate (EM) is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin. EM has been reported to be active in metastatic breast cancer. In this paper, we report efficacy and safety of data of EM in a retrospective, real-world series of patients with poor prognosis, hormone-refractory, or triple-negative metastatic breast cancer. MATERIALS AND METHODS: The analysis was carried out at 4 interrelated oncology centers. EM was delivered at the dose of 1.4 mg/m2 in 100 mL of normal saline over 2 to 5 minutes on days 1 and 8 every 21 days. EM was continued until disease progression or unacceptable toxicity. Side effects were reported every cycle as per standard clinical practice and graded according to NCI-CTCAE, version 4.0. Time-to-progression and overall survival were reported. RESULTS: In this series of 90 patients the overall response rate was 22%, and 21% and 23% in the hormonal-resistant group and the triple-negative one, respectively. Stable disease was recorded in 24%, 21%, and 27%, respectively, in the whole series, the hormonal-resistant group, and the triple-negative one, respectively. Time-to-progression was 3.5 months (range, 1 to 22 mo) in the whole series and 3.0 months (range, 1 to 14.7 mo) and 3.4 months (range, 2.2 to 16.2 mo) in the hormonal-resistant group and the triple-negative one, respectively. Overall survival reached a median of 11.4 months. CONCLUSIONS: This multicenter study, albeit retrospective, demonstrates the activity of this combination as third-line chemotherapy option in a challenging clinical setting such as triple-negative or hormone-resistant patients with breast cancer progressing after several lines of hormonal manipulations.


Assuntos
Antineoplásicos/uso terapêutico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Furanos/administração & dosagem , Furanos/efeitos adversos , Humanos , Cetonas/administração & dosagem , Cetonas/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/mortalidade , Neoplasias Hormônio-Dependentes/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
10.
Anticancer Res ; 41(2): 845-858, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517290

RESUMO

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) remains difficult to treat and new molecular targets are needed. Here, we investigated the impact of glycosyltransferase genes on TNBC patient survival. PATIENTS AND METHODS: mRNA expression levels of 101 glycosyltransferase genes in TNBC patients were compared for correlation with patient survival using The Cancer Genome Atlas data. An antibody to ß-3-N-acetylgluco-saminyltransferase 8 (B3GNT8) was applied to investigate B3GNT8 protein distribution and expression levels in 23 TNBC surgical specimens. RESULTS: B3GNT8 mRNA levels inversely correlated with relapse-free survival (p<0.01) and overall survival (p<0.05) in TNBC patients. Anti-B3GNT8 antibody binding was observed as dots in the cytoplasm of cancer cells. These dots were supposed to correspond to B3GNT8 protein in tumour cells, but their number was smaller in relapsed patients than in non-relapsed patients. CONCLUSION: B3GNT8 mRNA expression levels in TNBC tumour tissues are potentially useful in distinguishing patients with favourable and poor clinical outcomes.


Assuntos
Citoplasma/metabolismo , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
11.
Anticancer Res ; 41(2): 1077-1082, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517318

RESUMO

BACKGROUND/AIM: This study examined the prognostic impact of the past history of breast cancer screening within the last 2 years (PH-BCS), for patients with triple negative breast cancer (TNBC), a subtype that carries extremely poor prognosis. PATIENTS AND METHODS: Eighty-six consecutive cases with TNBC, who underwent surgery at our faculty from 2009 to 2015, were divided into two groups according to PH-BCS. Prognostic analyses for disease-free survival and overall survival between the two groups were performed. RESULTS: The positive PH-BCS group (n=44) had a significantly better prognoses than the negative PH-BCS group (n=42) (p<0.001). No recurrent cases were observed in the positive PH-BCS group. In the negative PH-BCS group, tumor and node status and chemotherapy were indicated as significant prognostic factors, and further step-wise multivariate analysis revealed only node status as a significant prognostic factor. CONCLUSION: Breast cancer screening at least every 2 years may improve the prognosis of TNBC.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Tratamento Farmacológico , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
12.
Medicine (Baltimore) ; 99(50): e23418, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327268

RESUMO

BACKGROUND: Triple negative breast cancer affects 10% to 20% of all women diagnosed with breast cancer. Due to its characteristics, treatment strategies are limited and metastatic recurrences are common in the first 5 years after treatment. However, not all patients affected by this disease develop metastases. Tumor-infiltrating lymphocytes have shown to be reliable predictive biomarkers of treatment response and metastatic recurrences. However, we need to develop simpler and faster ways to predict response to cytotoxic treatment and the possibility of eventual cancer relapse by identifying new biomarkers. Recently, new studies are emerging, suggesting a predictive role of circulating blood cells in different types of cancer. In this study, we will assess the correlation between tumor-infiltrating lymphocytes and different elements of the blood count in patients diagnosed with triple negative breast cancer. METHODS: The main objective of this study is to evaluate the correlation between the peripheral neutrophil-to-lymphocyte ratio and the amount of tumor-infiltrating lymphocytes, assessed in triple negative breast cancer patients at diagnosis. Secondary objectives include evaluation of the correlation between tumor-infiltrating lymphocytes at diagnosis and the baseline absolute neutrophil, lymphocyte, and platelet counts, as well as the platelet-to-lymphocyte ratio. The triple negative breast cancer patients will be enrolled in the PERCEPTION trial during the first year after the treatment completion. Two supplementary blood tests, at 12 months after the end of treatment and at the time of the first metastatic recurrence, will be performed. DISCUSSION: The discovery of new prognostic and predictive biomarkers is crucial for triple negative breast cancer. We set up the PERCEPTION clinical trial in order to evaluate certain blood counts as early biomarkers and to assess their correlation with tumor-infiltrating lymphocytes. Demonstration of comparative predictive and/or prognostic capacities of peripheral blood counts and tumor-infiltrating lymphocytes would allow introduction of the former as simple and cheap biomarkers in triple negative breast cancer patient management. TRIAL REGISTRATION: The PERCEPTION study has been registered in the French National Agency of Medical Security registry on the 2nd of July 2019 under the number 2019-A01861-56 and in the ClinicalTrials.org registry under the number NCT04068623.


Assuntos
Plaquetas/metabolismo , Neoplasias da Mama/sangue , Linfócitos do Interstício Tumoral/metabolismo , Neutrófilos/metabolismo , Neoplasias de Mama Triplo Negativas/sangue , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/mortalidade , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto Jovem
13.
Cochrane Database Syst Rev ; 10: CD013750, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084020

RESUMO

BACKGROUND: In a previous Cochrane Review, we found that for women with metastatic breast cancer unselected for triple-negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. In subgroup analyses, however, we found preliminary low-quality evidence of a survival benefit from platinum-based regimens for women with metastatic triple-negative breast cancer (mTNBC). This review updates the evidence from the mTNBC subgroup analyses in the previous Cochrane Review. OBJECTIVES: To assess the effects of platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with mTNBC. SEARCH METHODS: We obtained relevant studies published prior to 2015 and their extracted results from the mTNBC subgroup analysis in the previous Cochrane Review. We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov between 2015 and 27 September 2019. We identified further potentially relevant studies from previous trial reports, systematic reviews, and meta-analyses. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with mTNBC. Individual trials could compare one or more platinum-based regimens to one or more non-platinum regimens; hence there could be more 'treatment-comparisons' (i.e. platinum regimen versus non-platinum regimen comparison) than trials. Trial participants may have been purposely selected for mTNBC or inadvertently selected as a subgroup. DATA COLLECTION AND ANALYSIS: At least two independent reviewers assessed studies for eligibility and quality, and extracted all relevant data from each study. We derived hazard ratios (HRs) for time-to-event outcomes, where possible, and used fixed-effect models for meta-analyses. We analysed objective tumour response rates (OTRRs) and toxicities as binary (dichotomous) outcomes with risk ratios (RRs) used as measures of effects. We extracted quality of life data, if available. We used GRADE to rate the quality of evidence for time-to-event and tumour response outcomes. MAIN RESULTS: This review includes 13 treatment-comparisons involving 1349 women from 10 studies. Twelve of the 13 treatment-comparisons were included in one or more meta-analyses. Of the 13 treatment-comparisons, six and eight had published or provided time-to-event data on overall survival (OS) or progression-free survival/time to progression (PFS/TTP), respectively, that could be included in meta-analyses. Ten treatment-comparisons published or provided OTRR data that could be included in meta-analyses. Eight of the 13 treatment-comparisons were from studies that selected participants on the basis of mTNBC status, while the other five treatment-comparisons were from studies that reported mTNBC results as part of subgroup analyses. Analysis of six treatment-comparisons indicated that platinum-containing regimens may have provided a small survival benefit to mTNBC patients (HR 0.85, 95% CI 0.73 to 1.00; 958 women; moderate-quality evidence) with no evidence of heterogeneity (P = 0.41; I2 = 1%). Data from eight treatment-comparisons showed that platinum regimens may improve PFS/TTP (HR 0.77, 95% CI 0.68 to 0.88; 1077 women; very low-quality evidence). There was marked evidence of heterogeneity (P < 0.0001; I2 = 80%). There was also low-quality evidence of better tumour response for platinum recipients (RR 1.40, 95% CI 1.22 to 1.59; 1205 women) with some evidence of heterogeneity (P = 0.01; I2 = 58%). The observed heterogeneity for the PFS/TTP and OTRR outcomes may reflect between-study differences and general difficulties in assessing tumour response, as well as the varying potencies of the comparators. Compared with women receiving non-platinum regimens: rates of grade 3 and 4 nausea/vomiting were higher for platinum recipients (RR 4.77, 95% CI 1.93 to 11.81; 655 women; low-quality evidence) and rates of grade 3 and 4 anaemia were higher for platinum recipients (RR 3.80, 95% CI 2.25 to 6.42; 843 women; low-quality evidence). In general, however, relatively few intervention-comparisons could be included in meta-analyses for adverse events. None of the studies reported quality of life. AUTHORS' CONCLUSIONS: For women with mTNBC, there was moderate-quality evidence of a small survival benefit from platinum-based regimens compared to non-platinum regimens. This finding is consistent with findings of a PFS/TTP benefit and improved tumour response from platinum-based regimens. These potential benefits, however, should be weighed against previously identified excess toxicities from platinum-based regimens, particularly regimens containing cisplatin. Further randomised trials of platinum-based regimens among women with mTNBC are required.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Viés , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Náusea/induzido quimicamente , Oxaliplatina/efeitos adversos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Vômito/induzido quimicamente
14.
Medicine (Baltimore) ; 99(37): e21861, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925722

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. Accumulating evidence showed long non-coding RNAs (lncRNAs) are abnormally expressed in TNBC and could be valuable prognostic tools for TNBC patients. This study aims to research the prognostic value of lncRNAs in TNBC, using the meta-analysis method. METHODS: We performed a detailed literature search on Pubmed, Scopus, and Web of Science for studies on the prognostic value of lncRNAs in TNBC. The meta-analysis method was used to determine the relationship between lncRNAs expression and survival of TNBC patients. RESULTS: A total of 2803 TNBC patients and 24 lncRNAs from 27 different articles were included in the present study. Subgroup analysis demonstrated that overexpression of lncRNAs in a group that is upregulated in TBNC showed a significant association with poor overall survival (HR = 1.86, 95%CI = 1.45-2.27, I = 41.9%) and disease-free survival (HR = 1.85, 95%CI = 1.37-2.33, I = 0%). Conversely, overexpression of lncRNAs in a downregulation group was markedly related to good overall survival (HR = 0.60, 95%CI = 0.43-0.77, I = 28.6%). Moreover, expression of lncRNA SNHG12, MALAT1, HOTAIR, HIF1A-AS2, HULC, LINC00096, ZEB2-AS1, LUCAT1, and LINC000173 showed a marked correlation with positive lymph node metastasis (LNM), while lncRNA MIR503HG, GAS5, TCONS_l2_00002973 showed the opposite effect. High expression level of MALAT1, HIF1A-AS2, HULC, LINC00096, ADPGK-AS1, ZEB2-AS1, LUCAT1 were positively correlated with distant metastasis (DM), while lncRNA MIR503HG showed the opposite effect. In addition, the mechanisms of lncRNAs in TNBC were summarized. CONCLUSIONS: This meta-analysis demonstrated that abnormally expressed lncRNA were significantly associated with the survival of TNBC patients and may serve as biomarkers and therapeutic targets for TNBC prognosis.


Assuntos
RNA Longo não Codificante/análise , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico
15.
Medicine (Baltimore) ; 99(31): e21333, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756119

RESUMO

This study aimed to evaluate the imaging findings and prognostic factors after whole-brain radiotherapy in patients with carcinomatous meningitis from breast cancer.A retrospective analysis of imaging data and prognostic factors was performed in patients treated with whole-brain radiotherapy or whole-brain/spine radiotherapy immediately after the first diagnosis of carcinomatous meningitis from breast cancer at our hospital from January 1, 2010 to December 31, 2018. Statistical significance was set at P < .05 (two-tailed).All patients (n = 31) were females with the mean age of 58.0 ±â€Š11.0 years. The breast cancer subtypes were luminal (n = 14, 45.1%), human epidermal growth factor receptor 2 (HER2)-positive (n = 9, 29.0%), and triple-negative (n = 8, 26.0%) breast cancer. Brain metastasis and abnormal contrast enhancement in the sulci were observed in 21 (67.7%) and 24 (80.6%) patients, respectively. The median survival time after cancerous meningitis diagnosis was 62 (range, 6-657) days. Log-rank test showed significant differences in median survival time after cancerous meningitis diagnosis: 18.0 days for subjects treated with 30 Gy in < 10 fractions (n = 7) vs 78.5 days for subjects treated with 30 Gy in ≥10 fractions (n = 24) (P < .01) and 23.0 days for the triple-negative subtype vs 78.5 days for the other subtype (P < .01) groups. Univariate analysis using the Cox regression model showed significant differences in median survival time after cancerous meningitis diagnosis between the group treated with 30 Gy in <10 fractions and the group treated in ≥10 fractions (hazard ratio [HR] 0.08, 95% confidence interval [CI], 0.03-0.26; P < .01), and between the triple-negative subtype and the other subtypes (HR = 5.48; 95% CI, 1.88-16.0; P < .01) groups.Discontinuation of whole-brain radiotherapy and the presence of triple-negative breast cancer were indicators of poor prognosis.


Assuntos
Neoplasias Encefálicas/secundário , Carcinomatose Meníngea/secundário , Neoplasias de Mama Triplo Negativas/mortalidade , Idoso , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Relação Dose-Resposta à Radiação , Feminino , Humanos , Imageamento por Ressonância Magnética , Carcinomatose Meníngea/diagnóstico por imagem , Carcinomatose Meníngea/radioterapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias de Mama Triplo Negativas/patologia
16.
Medicine (Baltimore) ; 99(18): e19986, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358373

RESUMO

BACKGROUND: The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and explore the key pathways and genes of TNBC. METHODS: The gene expression profiling (GSE86945, GSE86946 and GSE102088) data were obtained from Gene Expression Omnibus Datasets, DEGs were identified by using R software, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools, and the protein-protein interaction (PPI) network of the DEGs was constructed by the STRING database and visualized by Cytoscape software. Finally, the survival value of hub DEGs in breast cancer patients were performed by the Kaplan-Meier plotter online tool. RESULTS: A total of 2998 DEGs were identified between TNBC and health breast tissue, including 411 up-regulated DEGs and 2587 down-regulated DEGs. GO analysis results showed that down-regulated DEGs were enriched in gene expression (BP), extracellular exosome (CC), and nucleic acid binding, and up-regulated were enriched in chromatin assembly (BP), nucleosome (CC), and DNA binding (MF). KEGG pathway results showed that DEGs were mainly enriched in Pathways in cancer and Systemic lupus erythematosus and so on. Top 10 hub genes were picked out from PPI network by connective degree, and 7 of top 10 hub genes were significantly related with adverse overall survival in breast cancer patients (P < .05). Further analysis found that only EGFR had a significant association with the prognosis of triple-negative breast cancer (P < .05). CONCLUSIONS: Our study showed that DEGs were enriched in pathways in cancer, top 10 DEGs belong to up-regulated DEGs, and 7 gene connected with poor prognosis in breast cancer, including HSP90AA1, SRC, HSPA8, ESR1, ACTB, PPP2CA, and RPL4. These can provide some guidance for our research on the diagnosis and prognosis of TNBC, and further research is needed to evaluate their value in the targeted therapy of TNBC.


Assuntos
Mineração de Dados/métodos , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias de Mama Triplo Negativas/genética , Bases de Dados Genéticas , Regulação para Baixo , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/mortalidade , Regulação para Cima
17.
J Surg Res ; 254: 83-90, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32422430

RESUMO

BACKGROUND: Trials demonstrate equivalent survival for breast cancers treated with neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC). However, these were conducted before the recognition of the importance of receptor subtype for survival and chemotherapy response. Therefore, chemotherapy timing may impact survival for certain receptor subtypes. A scoping review of studies assessing outcomes by chemotherapy timing based on receptor subtype was conducted to evaluate gaps in the existing literature. METHODS: Three databases were searched in February 2019 with terms related to breast cancer, NAC/AC, and survival. Inclusion criteria were original peer-reviewed studies published in English after 1989 comparing breast cancer outcomes for females based on chemotherapy timing. Studies/sections of studies lacking outcomes by receptor subtype or including patients missing appropriate targeted therapy were excluded. RESULTS: Of 7354 articles, 262 abstracts and 60 full texts were reviewed. Three studies met criteria. All were single-institution retrospective studies analyzing outcomes for triple negative (TN) patients with one study also examining luminal A patients. Significant differences in clinical characteristics existed between patients selected for NAC versus AC. Two studies demonstrated no survival difference by chemotherapy timing for TN patients, with the third showing improved likelihood of survival after AC for TN patients. No difference was seen for patients with luminal A cancer. CONCLUSIONS: Our scoping review reveals a significant gap in the existing literature regarding optimal timing of chemotherapy for modern-era patients receiving targeted therapy based on receptor subtype. Review of the identified studies identified methodological challenges to answering this question through observational study designs.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Receptores Citoplasmáticos e Nucleares/classificação , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Feminino , Humanos , Antígeno Ki-67/análise , Terapia de Alvo Molecular/métodos , Recidiva Local de Neoplasia/epidemiologia , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade
18.
Breast Cancer Res ; 22(1): 42, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375854

RESUMO

BACKGROUND: Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis. METHODS: Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC). RESULTS: Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups. CONCLUSIONS: Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.


Assuntos
Colágeno/ultraestrutura , Matriz Extracelular/ultraestrutura , Processamento de Imagem Assistida por Computador/métodos , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral , Colágeno/metabolismo , Intervalo Livre de Doença , Matriz Extracelular/metabolismo , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Taxa de Sobrevida , Análise Serial de Tecidos/métodos
19.
PLoS One ; 15(4): e0231712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298355

RESUMO

PURPOSE: Black/African American (AA) women are twice as likely to be diagnosed with triple negative breast cancer (TNBC) compared to whites, an aggressive breast cancer subtype associated with poor prognosis. There are no routinely used targeted clinical therapies for TNBC; thus there is a clear need to identify prognostic markers and potential therapeutic targets. METHODS: We evaluated expression of 27,016 genes in 155 treatment-naïve TN tumors from AA women in Detroit. Associations with survival were evaluated using Cox proportional hazards models adjusting for stage and age at diagnosis, and p-values were corrected using a false discovery rate. Our validation sample consisted of 494 TN tumors using four publically available data sets. Meta-analyses were performed using summary statistics from the four validation results. RESULTS: In the Detroit AA cohort, CLCA2 [Hazard ratio (HR) = 1.56, 95% confidence interval (CI) 1.31-1.86, nominal p = 5.1x10-7, FDR p = 0.014], SPIC [HR = 1.47, 95%CI 1.26-1.73, nominal p = 1.8x10-6, FDR p = 0.022], and MIR4311 [HR = 1.57, 95% CI 1.31-1.92, nominal p = 2.5x10-5, FDR p = 0.022] expression were associated with overall survival. Further adjustment for treatment and breast cancer specific survival analysis did not substantially alter effect estimates. CLCA2 was also associated with increased risk of death in the validation cohorts [HR = 1.14, 95% CI 1.05-1.24, p = 0.038, p-heterogeneity = 0.88]. CONCLUSIONS: We identified CLCA2 as a potential prognostic marker for TNBC in AA women.


Assuntos
Afro-Americanos , Canais de Cloreto/metabolismo , Neoplasias de Mama Triplo Negativas/etnologia , Neoplasias de Mama Triplo Negativas/mortalidade , Biomarcadores Tumorais , Canais de Cloreto/genética , Estudos de Coortes , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
20.
PLoS One ; 15(4): e0231711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298357

RESUMO

Actively growing tumors are often histologically associated with Ki67 positivity, while the detection of invasiveness relies on non-quantitative pathologic evaluation of mostly advanced tumors. We recently reported that reduced expression of the Ca2+-dependent membrane-binding annexin A6 (AnxA6) is associated with increased expression of the Ca2+ activated RasGRF2 (GRF2), and that the expression status of these proteins inversely influence the growth and motility of triple negative breast cancer (TNBC) cells. Here, we establish that the reciprocal expression of AnxA6 and GRF2 is at least in part, dependent on inhibition of non-selective Ca2+ channels in AnxA6-low but not AnxA6-high TNBC cells. Immunohistochemical staining of breast cancer tissues revealed that compared to non-TNBC tumors, TNBC tumors express lower levels of AnxA6 and higher Ki67 expression. GRF2 expression levels strongly correlated with high Ki67 in pretreatment biopsies from patients with residual disease and with residual tumor size following chemotherapy. Elevated AnxA6 expression more reliably identified patients who responded to chemotherapy, while low AnxA6 levels were significantly associated with shorter distant relapse-free survival. Finally, the reciprocal expression of AnxA6 and GRF2 can delineate GRF2-low/AnxA6-high invasive from GRF2-high/AnxA6-low rapidly growing TNBCs. These data suggest that AnxA6 may be a reliable biomarker for distant relapse-free survival and response of TNBC patients to chemotherapy, and that the reciprocal expression of AnxA6 and GRF2 can reliably delineate TNBCs into rapidly growing and invasive subsets which may be more relevant for subset-specific therapeutic interventions.


Assuntos
Anexina A6/metabolismo , Canais de Cálcio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Fatores ras de Troca de Nucleotídeo Guanina/metabolismo , Animais , Anexina A6/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Antígeno Ki-67/metabolismo , Camundongos , Metástase Neoplásica/genética , Prognóstico , Transplante Heterólogo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade , Fatores ras de Troca de Nucleotídeo Guanina/genética
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