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2.
Rev Assoc Med Bras (1992) ; 67(8): 1167-1171, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34669864

RESUMO

OBJECTIVE: To explore the values of automated breast volume scanning (ABVS) combined with shear wave elastography (SWE) in the differential diagnosis of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-positive breast cancers (HER2+BC). METHODS: In this study, 28 patients with TNBC and 32 patients with HER2+BC were enrolled. The characteristics of ABVS and virtual touch quantification (VTQ) in SWE of all patients were reviewed. The multivariate logistic regression analysis was carried out and the receiver operating characteristic curves of ABVS and ABVS+VTQ were drawn. RESULTS: In ABVS imaging, the microcalcification, posterior echo, internal echo, shape, and edge had significant difference between TNBC and HER2+BC groups (p<0.05). The regular shape was the independent factor for TNBC (p=0.04, odds ratio [OR]=4.479), and the microcalcification in mass was the independent factor for HER2+BC (p=0.01, OR=2.997). In VTQ imaging, the shear wave velocity (SWV)max, SWVmin, and SWVmean in TNBC group were significantly lower than those in HER2+BC group (p<0.001). The sensitivity, specificity, and accuracy of ABVS+VTQ in diagnosing TNBC were higher than those of ABVS alone. CONCLUSIONS: ABVS combined with SWE has certain advantages in differentiating TNBC from HER2+BC, which is helpful for the treatment planning and prognosis judgment.


Assuntos
Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Neoplasias de Mama Triplo Negativas , Mama , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Curva ROC , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem
3.
Molecules ; 26(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34500557

RESUMO

In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Mebendazol/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Biomarcadores Tumorais/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo
4.
J Biomed Nanotechnol ; 17(8): 1554-1563, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544533

RESUMO

Clinical treatment of triple negative breast cancer (TNBC) is very poor for lack of effective treatment combination selection. Protein C receptor (PROCR) is a novel cancer stem marker in TNBC patients tumor tissues. Developed based on peptide BP10 with affinity to PROCR as a targeting element, constructing a peptide drug conjugate of BP10 covalently coupling doxorubicin with disulfide bonds. This study demonstrated that the constructed BP10-DOX can selectively target Triplenegative breast cancer cells expressing PROCR and controlled release of DOX in response to the GSH environment. Moreover, BP10-DOX improves the therapeutic efficiency on MDA-MB-231 cells in vitro. Further evidence obtained from in vivo xenograft experiments revealed that administration of BP10-DOX enhanced the antitumor efficacy. This study developed a promising chemotherapy strategy for TNBC.


Assuntos
Preparações Farmacêuticas , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Humanos , Peptídeos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
5.
Nanoscale ; 13(31): 13375-13389, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477743

RESUMO

Owing to its aggressive biological behavior, the lack of specific targets, and the strong therapeutic resistance of triple negative breast cancer (TNBC), current therapeutic strategies are still limited. The combination of multiple treatments has been confirmed as a promising strategy for TNBC therapy. However, the efficacy of combination therapy can be restricted due to increasing therapeutic resistance to various treatments. Herein, we constructed a nanodiamond (ND)-based nanoplatform for augmented mild-temperature photothermal/chemo combination therapy against TNBC, weakening the therapeutic resistance via autophagy inhibition enabled by the NDs. A layer-by-layer self-assembly approach was utilized to construct the ND-based nanoplatform. First, the NDs were modified with protamine sulphate (PS). Meanwhile, the photosensitizer indocyanine green (ICG) and the HSP70 small molecule inhibitor apoptozole (APZ) could be synchronously incorporated to form positively charged PS@ND (ICG + APZ). Then negatively charged hyaluronic acid (HA) was assembled onto the outer face of PS@ND (ICG + APZ) to form the NPIAs. Finally, the positively charged small molecule anti-cancer drug doxorubicin (DOX) could be adsorbed onto the surface of the NPIAs through electrostatic interactions (NPIADs). The resulting NPIADs could be triggered by NIR laser irradiation to exhibit enhanced mild-temperature photothermal therapy (PTT) effects via suppressing the expression of HSP70, and PTT combined with chemotherapy could further enhance the anti-tumor efficacy. Subsequently, the sensitivity of MDA-MB-231 cells could be significantly improved through the weakening of the thermal/drug resistance via autophagy inhibition, leading to augmented combination therapy that is efficient both in vitro and in vivo. Furthermore, the NPIADs could be used as a theranostic nanoplatform for fluorescence (FL) and photoacoustic (PA) imaging. Taken together, this study demonstrated a multifunctional ND-based nanoplatform for FL/PA imaging-guided augmented mild-temperature photothermal/chemo combination therapy via an autophagy regulation strategy against TNBC.


Assuntos
Hipertermia Induzida , Nanodiamantes , Nanopartículas , Neoplasias de Mama Triplo Negativas , Autofagia , Doxorrubicina/farmacologia , Humanos , Fototerapia , Temperatura , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
6.
World J Surg Oncol ; 19(1): 264, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34474671

RESUMO

BACKGROUND: Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. METHODS: PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). RESULTS: Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by "MD Anderson Cancer Center Residual Cancer Burden Index" (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. CONCLUSIONS: Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Antígeno B7-H1/metabolismo , Humanos , Linfócitos do Interstício Tumoral , Terapia Neoadjuvante , Neoplasia Residual , Prognóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
7.
Br J Radiol ; 94(1126): 20210188, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478336

RESUMO

OBJECTIVES: To explore the predictive value of radiomics nomogram using pretreatment ultrasound for disease-free survival (DFS) after resection of triple negative breast cancer (TNBC). METHODS AND MATERIALS: A total of 486 TNBC patients from 3 different institutions were consecutively recruited for this study. They were categorized into the primary cohort (n = 216), as well as the internal validation cohort (n = 108) and external validation cohort (n = 162). In primary cohort, least absolute shrinkage and selection operator logistic regression algorithm was used to select recurrence-related radiomics features extracted from the breast tumor and peritumor regions, and a radiomics signature was constructed derived from the grayscale ultrasound images. A radiomic nomogram integrating independent clinicopathological variables and radiomic signature was established with uni- and multivariate cox regressions. The predictive nomogram was validated using an internal cohort and an independent external cohort regarding abilities of discrimination, calibration and clinical usefulness. RESULTS: The patients with higher Rad-score had a worse prognostic outcome than those with lower Rad-score in primary cohort and two validation cohorts (All p < 0.05).The radiomics nomogram indicated more effective prognostic performance compared with the clinicopathological model and tumor node metastasis staging system (p < 0.01), with a training C-index of 0.75 (95% confidence interval (CI), 0.71-0.80), an internal validation C-index of 0.73 (95% CI, 0.69-0.78) and an external validation 0.71 (95% CI,0.66-0.76). Moreover, the calibration curves revealed a good consistency for survival prediction of the radiomics model. CONCLUSIONS: The ultrasound-based radiomics signature was a promising biomarker for risk stratification for TNBC patients. Furthermore, the proposed radiomics modal integrating the optimal radiomics features and clinical data provided individual relapse risk accurately. ADVANCES IN KNOWLEDGE: The radiomics model integrating radiomic signature and independent clinicopathological variables could improve individual prognostic evaluation and facilitate therapeutic decision-making, which demonstrated the incremental value of the radiomics signature for prognostic prediction in TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/mortalidade , Ultrassonografia Mamária/métodos , Idoso , Algoritmos , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/cirurgia
8.
Cesk Patol ; 57(3): 161-166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34551565

RESUMO

Evaluation of tumor infiltrating lymphocytes (TIL) is gaining importance in many cancers not only because of their prognostic, but also predictive significance. One of the tumors in which the evaluation of TIL is of prognostic importance and has potential predictive impact on the modification of treatment procedures is breast cancer, especially its so-called triple negative, and HER2 positive variants.The aim of this review is to provide an overview of the issue of TIL evaluation in breast cancer, focusing not only on the clinical significance of this evaluation, but especially on the methodological aspects of evaluation and standardized reporting of the results.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Linfócitos do Interstício Tumoral , Prognóstico , Receptor ErbB-2
9.
Nat Commun ; 12(1): 5389, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508101

RESUMO

Conditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24COE) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24COE metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24COE gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling reveal Met as a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of these pathways in primary Trim24COE tumor cells and TRIM24-PROTAC treatment of MpBC TNBC PDX tumorspheres decreased cellular viability, suggesting potential in therapeutically targeting TRIM24 and its regulated pathways in TRIM24-expressing TNBC.


Assuntos
Carcinossarcoma/genética , Proteínas de Transporte/genética , Neoplasias Mamárias Experimentais/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Neoplasias de Mama Triplo Negativas/genética , Animais , Mama/patologia , Carcinossarcoma/patologia , Proteínas de Transporte/metabolismo , Ensaios Clínicos como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-met/genética , RNA-Seq , Análise de Célula Única , Fatores de Transcrição/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Cancer Treat Rev ; 100: 102283, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34530283

RESUMO

PURPOSE: The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established. METHODS: A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting and study design. RESULTS: Fourteen studies comprising 3518 patients met the inclusion criteria. Median follow up was 56.2 months. All studies reported DFS and 9 studies (64%) reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.56-0.89; p = 0.03). However, OS was no different (HR 0.98, 95% CI 0.75-1.27; p = 0.87). There was a non-significant difference between platinum exposure in the adjuvant compared to neoadjuvant setting for both DFS (HR 0.75 vs 0.62, p = 0.43) and for OS (HR 0.90 vs 1.10, p = 0.58). The addition of platinum was associated with more thrombocytopenia and all-grade neuropathy and non-significant increases in neutropenia and grade 3-4 neuropathy. CONCLUSIONS: Platinum-based treatment improves DFS but not OS. The reporting of toxicity was suboptimal, but in general adding platinum increased toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. Platinum-based chemotherapy cannot be recommended in unselected patients with early TNBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Humanos , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias de Mama Triplo Negativas/patologia
11.
Nat Commun ; 12(1): 5668, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580291

RESUMO

Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack of response to ICI, we analyze 681 TNBCs for spatial immune cell contextures in relation to clinical outcomes and pathways of T cell evasion. Excluded, ignored and inflamed phenotypes can be captured by a gene classifier that predicts prognosis of various cancers as well as anti-PD1 response of metastatic TNBC patients in a phase II trial. The excluded phenotype, which is associated with resistance to anti-PD1, demonstrates deposits of collagen-10, enhanced glycolysis, and activation of TGFß/VEGF pathways; the ignored phenotype, also associated with resistance to anti-PD1, shows either high density of CD163+ myeloid cells or activation of WNT/PPARγ pathways; whereas the inflamed phenotype, which is associated with response to anti-PD1, revealed necrosis, high density of CLEC9A+ dendritic cells, high TCR clonality independent of neo-antigens, and enhanced expression of T cell co-inhibitory receptors.


Assuntos
Resistencia a Medicamentos Antineoplásicos/imunologia , Inibidores de Checkpoint Imunológico/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linfócitos T/imunologia , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Mama/imunologia , Mama/patologia , Mama/cirurgia , Estudos de Coortes , Conjuntos de Dados como Assunto , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunofenotipagem , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Mastectomia , Terapia Neoadjuvante/métodos , Prognóstico , RNA-Seq , Receptores de Superfície Celular/metabolismo , Análise Espacial , Linfócitos T/metabolismo , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Evasão Tumoral , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Via de Sinalização Wnt/imunologia
12.
Future Oncol ; 17(30): 3911-3924, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467774

RESUMO

Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short. Metastatic breast cancer means the breast cancer has spread to other parts of the body. Triple negative means the breast cancer does not have 3 common proteins on the cell surface called receptors. This is a summary of the ASCENT study, published in the New England Journal of Medicine in April 2021. This study compared Sacituzumab Govitecan with standard chemotherapy. Chemotherapy is a treatment that kills cancer cells or stops them from dividing. 529 people with mTNBC took part in the study across 7 countries. All who took part had already received 2 previous chemotherapies, which stopped working for their cancer. The study showed that patients who took Sacituzumab Govitecan lived longer than those who took a different chemotherapy while on the study. Tumors shrank in more patients who took Sacituzumab Govitecan than in patients who took chemotherapy. In general, patients who took Sacituzumab Govitecan experienced more side effects. This included low levels of a type of white blood cell known as neutrophils (neutropenia) and loose or watery stool (diarrhea). Use of supportive care lessened these side effects. This summary also includes insights and perspectives from 2 breast cancer patient advocates. ClinicalTrials.gov NCT number: NCT02574455. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here.


Assuntos
Imunoconjugados , Neoplasias de Mama Triplo Negativas , Anticorpos Monoclonais Humanizados , Camptotecina/análogos & derivados , Humanos , Idioma , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
13.
BMC Cancer ; 21(1): 1051, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563146

RESUMO

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. METHODS: We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. RESULTS: Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. CONCLUSIONS: Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies.


Assuntos
Composição Corporal , Neoplasias da Mama/etiologia , Adulto , Estatura , Índice de Massa Corporal , Peso Corporal , Neoplasias da Mama/química , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Nigéria , Razão de Chances , História Reprodutiva , Fatores de Risco , Neoplasias de Mama Triplo Negativas/química , Neoplasias de Mama Triplo Negativas/etiologia
14.
BMC Cancer ; 21(1): 1062, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565331

RESUMO

BACKGROUND: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). METHODS: We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. CONCLUSIONS: BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteína BRCA2/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/sangue , Fatores de Transcrição de Zíper de Leucina Básica/genética , Mama/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Bases de Dados Factuais , Exossomos/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Prognóstico , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética
15.
BMC Med ; 19(1): 190, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465315

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown. METHODS: Data from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings. RESULTS: HRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e-04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001). CONCLUSIONS: These findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.


Assuntos
Neoplasias de Mama Triplo Negativas , Antraciclinas , Ciclofosfamida , Humanos , Reparo de DNA por Recombinação , Taxoides , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética
16.
BMC Cancer ; 21(1): 1026, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525987

RESUMO

BACKGROUND: Current treatment methods for patients with triple-negative breast cancer (TNBC) are very limited, and the prognosis of TNBC is relatively poor. It has been reported that glucose transporter 1 (GLUT1) is overexpressed in breast cancer cells; however, its association with the prognosis is mostly unclear. Moreover, retinoblastoma gene 1 (RB1) might be used as a biomarker for the sensitivity of breast cancer cells to GLUT1 inhibitors, which brought us to the hypothesis that there might be a close correlation between the expression of GLUT1-4 and the expression of RB1. METHODS: In this study, we systematically analyzed the co-expression of GLUT1-4 and the influence of GLUT1-4 gene expression on the prognosis of breast cancer using data mining methods. We also explored possible relationships between GLUT1-4 and RB1 expression in breast cancer tissues. We used public databases such as ONCOMINE, GEPIA, LinkedOmics, and COEXPEDIA. RESULTS: According to the results, the mRNA expression of SLC2A1 was significantly higher in breast cancer, while the expression levels of SLC2A2-4 were downregulated. The results also indicate that GLUT1 expression does not have significant influence on the overall survival of patients with breast cancer. The mRNA expression of SLC2A1 and RB1 is significantly correlated, which means that tissues with high RB1 mRNA expression might have relatively higher mRNA expression of SLC2A1; however, further study analyzing their roles in the expression regulation pathways with human samples is needed to verify the hypothesis. CONCLUSIONS: The mRNA expression of SLC2A1 was significantly higher in breast cancer. The overall survival of breast cancer patients wasn't significantly correlated with GLUT1-4 expression. The mRNA expression of SLC2A1 and RB1 is significantly correlated according to the analysis conducted in LinkedOmics. It provides reference for future possible individualized treatment of TNBC using GLUT1 inhibitors, especially in patients with higher mRNA expression of RB1. Further study analyzing the roles of these two genes in the regulation pathways is needed.


Assuntos
Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Proteínas de Ligação a Retinoblastoma/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Ubiquitina-Proteína Ligases/metabolismo , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Regulação para Baixo , Feminino , Genes do Retinoblastoma , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 4/genética , Humanos , Prognóstico , RNA Mensageiro/metabolismo , Proteínas de Ligação a Retinoblastoma/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Ubiquitina-Proteína Ligases/genética , Regulação para Cima
17.
Breast Cancer Res Treat ; 189(3): 653-663, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34487293

RESUMO

PURPOSE: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)-expressing invasive breast cancer. METHODS: This retrospective, non-interventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathological characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-low (1% to 10%) and ER-high (> 10%) according to the Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test. RESULTS: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-low tumors: 63 (53.8%) of whom had HER2- tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-high/HER2- cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-low/HER2- (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. CONCLUSION: Patients with ER-low/HER2- breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-low/HER2- disease.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Prevalência , Prognóstico , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , República da Coreia/epidemiologia , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/terapia
18.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502091

RESUMO

Triple-negative breast cancer (TNBC) tends to metastasize to the brain, a step that worsens the patient's prognosis. The specific hallmarks that determine successful metastasis are motility and invasion, microenvironment modulation, plasticity, and colonization. Zinc, an essential trace element, has been shown to be involved in all of these processes. In this work, we focus our attention on the potential role of zinc during TNBC metastasis. We used MDA-MB-BrM2 (BrM2) cells, a brain metastasis model derived from the parental TNBC cell line MDA-MB-231. Our studies show that BrM2 cells had double the zinc content of MDA-MB-231 cells. Moreover, exploring different metastatic hallmarks, we found that the zinc concentration is especially important in the microenvironment modulation of brain metastatic cells, enhancing the expression of SerpinB2. Furthermore, we show that zinc promotes the tumorigenic capacity of breast cancer stem cells. In addition, by causing a disturbance in MDA-MB-231 zinc homeostasis by overexpressing the Zip4 transporter, we were able to increase tumorigenicity. Nevertheless, this strategy did not completely recapitulate the BrM2 metastatic phenotype. Altogether, our work suggests that zinc plays an important role in the transformative steps that tumoral cells take to acquire tumorigenic potential and niche specificity.


Assuntos
Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral , Zinco/metabolismo , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Inibidor 2 de Ativador de Plasminogênio/genética , Inibidor 2 de Ativador de Plasminogênio/metabolismo
19.
Radiol Imaging Cancer ; 3(5): e200155, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34477453

RESUMO

Purpose To determine if amide proton transfer-weighted chemical exchange saturation transfer (APTW CEST) MRI is useful in the early assessment of treatment response in persons with triple-negative breast cancer (TNBC). Materials and Methods In this prospective study, a total of 51 participants (mean age, 51 years [range, 26-79 years]) with TNBC were included who underwent APTW CEST MRI with 0.9- and 2.0-µT saturation power performed at baseline, after two cycles (C2), and after four cycles (C4) of neoadjuvant systemic therapy (NAST). Imaging was performed between January 31, 2019, and November 11, 2019, and was a part of a clinical trial (registry number NCT02744053). CEST MR images were analyzed using two methods-magnetic transfer ratio asymmetry (MTRasym) and Lorentzian line shape fitting. The APTW CEST signals at baseline, C2, and C4 were compared for 51 participants to evaluate the saturation power levels and analysis methods. The APTW CEST signals and their changes during NAST were then compared for the 26 participants with pathology reports for treatment response assessment. Results A significant APTW CEST signal decrease was observed during NAST when acquisition at 0.9-µT saturation power was paired with Lorentzian line shape fitting analysis and when the acquisition at 2.0 µT was paired with MTRasym analysis. Using 0.9-µT saturation power and Lorentzian line shape fitting, the APTW CEST signal at C2 was significantly different from baseline in participants with pathologic complete response (pCR) (3.19% vs 2.43%; P = .03) but not with non-pCR (2.76% vs 2.50%; P > .05). The APTW CEST signal change was not significant between pCR and non-pCR at all time points. Conclusion Quantitative APTW CEST MRI depended on optimizing acquisition saturation powers and analysis methods. APTW CEST MRI monitored treatment effects but did not differentiate participants with TNBC who had pCR from those with non-pCR. © RSNA, 2021 Clinical trial registration no. NCT02744053 Supplemental material is available for this article. Keywords Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, MR-Imaging, Breast, Technical Aspects, Tumor Response, Technology Assessment.


Assuntos
Prótons , Neoplasias de Mama Triplo Negativas , Amidas , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Projetos Piloto , Estudos Prospectivos , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem
20.
In Vivo ; 35(5): 2531-2534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410939

RESUMO

BACKGROUND/AIM: The aim of the present study was to identify effective drugs for a highly-aggressive liver-metastasis of triple-negative breast cancer (TNBC) in a patient-derived orthotopic xenograft (PDOX) mouse model. Drugs tested were oral recombinant methioninase (o-rMETase), low-dose eribulin and their combination. MATERIALS AND METHODS: Patient-derived TNBC was implanted in the liver of nude mice by surgical hepatic implantation. Two weeks after transplantation, 32 mice were randomized (n=8 per group) into a phosphate-buffered saline vehicle-control group; o-rMETase-treatment group (100 units, o-rMETase, oral, daily for 2 weeks); eribulin-treatment group (0.05 mg/kg intraperitoneally once per week for 2 weeks); or combination-treatment group (100 units r-METase, oral, daily for 2 weeks + 0.05 mg/kg eribulin intraperitoneally once per week for 2 weeks). RESULTS: After 2 weeks, the three treatment groups exhibited significantly-inhibited TNBC growth in the liver compared to the vehicle-control group (p≤0.05). CONCLUSION: o-rMETase and low-dose eribulin monotherapy and their combination were efficacious against the highly-aggressive TNBC PDOX growing in the liver. The TNBC PDOX model can be used to identify highly-effective drugs for therapy of TNBC with liver metastasis.


Assuntos
Neoplasias Hepáticas , Neoplasias de Mama Triplo Negativas , Animais , Liases de Carbono-Enxofre , Furanos , Humanos , Cetonas , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Camundongos Nus , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
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