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1.
Isr Med Assoc J ; 22(10): 613-617, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33070484

RESUMO

BACKGROUND: An association was shown between thrombocytosis and future development of several cancers. OBJECTIVES: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer. METHODS: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years. RESULTS: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02). CONCLUSIONS: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Coagulação Intravascular Disseminada/epidemiologia , Trombocitose/epidemiologia , Idoso , Biomarcadores/análise , Plaquetas/fisiologia , Neoplasias da Mama/sangue , Estudos de Coortes , Comorbidade , Coagulação Intravascular Disseminada/sangue , Feminino , Humanos , Incidência , Israel , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Trombocitose/diagnóstico
2.
Anticancer Res ; 40(11): 6417-6428, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109580

RESUMO

BACKGROUND/AIM: Silencing mediator of retinoid and thyroid receptors (SMRT) is a nuclear corepressor in thyroid and estrogen hormones pathways. The aim was to evaluate SMRT expression in relation to thyroid hormone levels and prognostic markers in breast cancer (BC). PATIENTS AND METHODS: Serum and tumor tissues were obtained from 36 patients with benign breast disease (BBD) and 79 BC patients. SMRT expression was determined by immunohistochemistry. Free-triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured in serum. RESULTS: Higher FT4, lower FT3/FT4 ratio and higher expression of SMRT were found in BC compared to BBD (for all p<0.001). In BC, increased SMRT expression was associated with lower FT3 (p=0.028), higher tumor grade (p=0.031), increased KI67 proliferation index (p=0.015), higher risk of recurrence (p=0.014) and shorter disease-free survival (p=0.006). In multivariate analysis, SMRT overexpression and below-median levels of TSH were independent prognostic factors in BC. CONCLUSION: Elevated FT4 and decreased FT3/FT4 in BC patients suggest a role for thyroid hormones in malignant transformation. SMRT tumor overexpression is associated with lower FT3 levels, tumor proliferative activity and an aggressive clinical course.


Assuntos
Neoplasias da Mama/sangue , Correpressor 2 de Receptor Nuclear/genética , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Correpressor 2 de Receptor Nuclear/sangue , Prognóstico , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/sangue , Hormônios Tireóideos/genética
3.
Medicine (Baltimore) ; 99(43): e22890, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120836

RESUMO

Breast cancer is the most common malignancy affecting women worldwide. The insulin-like growth factor 1 (IGF-1) gene encodes a protein responsible for a wide variety of physiological processes, including differentiation and cell proliferation. Despite several studies on tumor tissues, no study has evaluated IGF-1 expression in the peripheral blood of women with recurrent breast cancer.In this cross-sectional study, IGF-1 expression in the peripheral blood of 146 women with breast cancer treated approximately 5 years ago was quantified by quantitative reverse transcription polymerase chain. The women were divided into 2 groups: non-recurrence (n = 85) and recurrence (n = 61). Statistical analysis of the data was performed using ANOVA, Mann-Whitney, and Chi-squared tests (P < .05).The results showed no significant difference in IGF-1 expression between the non-recurrence and recurrence groups (P = .988). In the subgroups of patients with lymph node involvement, no statistically significant difference was observed in IGF-1 expression between women with recurrence and those non-recurrence (P = .113). In patients without lymph node metastases, IGF-1 messenger ribonucleic acid (mRNA) expression levels were significantly higher in the non-recurrence group than in the recurrence group (P = .019). Furthermore, using the median IGF-1 mRNA expression as the cutoff point, it was obtained a statistically significant difference in tumor histological grade among women with recurrent breast cancer (P = .042).These data showed significantly higher IGF-1 expression in women without lymph node metastases in the non-recurrence group compared with the recurrence group. In addition, a significant difference was observed in median IGF-1 mRNA expression in relation to tumor histological grade in women with recurrent breast cancer.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fator de Crescimento Insulin-Like I/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Estudos de Casos e Controles , Diferenciação Celular , Proliferação de Células , Estudos Transversais , Feminino , Expressão Gênica/genética , Humanos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores/métodos , RNA Mensageiro/genética
4.
Maturitas ; 140: 64-71, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32972637

RESUMO

OBJECTIVES: Progesterone receptor membrane component-1 (PGRMC1) in breast cancer tissue has been suggested to predict a worse prognosis. The aim of this study was to assess for the first time whether PGRMC1 expressed in cancer tissue is associated with PGRMC1 blood concentrations and whether both are correlated with clinical tumour characteristics known to predict a worse outcome. METHODS: In total, 201 patients with invasive breast cancer and 65 with benign breast disease (control group) were recruited. PGRMC1 blood concentrations were measured by a recently developed ELISA, PGRMC1 in breast cancer tissue was assessed by immunohistochemistry, and the correlation between the two was calculated. Receiver-operating characteristic (ROC) curve analysis was used to assess area under the curve (AUC). Furthermore, PGRMC1 was correlated with tumour characteristics such as tumour diameter, tumour grade and metastatic status, and with known blood tumour markers. RESULTS: AUC for the breast cancer group was 0.713, which was significantly higher than in the control group (p < 0.01). Blood PGRMC1 concentrations had a strong (positive) correlation with tissue PGRMC1 expression (p < 0.01) but were not associated with serum tumour markers CEA, CA125, CA153 and TPS. Tissue PGRMC1, ER and cancer stage were positively associated with blood PGRMC1 (p < 0.05). CONCLUSIONS: As PGRMC1 expression levels in cancer tissue were significantly correlated with PGRMC1 in blood, and because concentrations in blood were also positively associated with breast tumour characteristics known to predict a worse prognosis, PGRMC1 may be valuable as a new tumour marker and may be superior to known tumour markers such as CEA, CA125, CA153 and TPS.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama , Proteínas de Membrana/sangue , Proteínas de Membrana/metabolismo , Receptores de Progesterona/sangue , Receptores de Progesterona/metabolismo , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Adulto Jovem
5.
Mol Carcinog ; 59(10): 1129-1139, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822091

RESUMO

For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single-cell RNA-sequencing (scRNA-seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size-exclusion membranes followed by scRNA-seq of enriched CTCs and carry-over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial-mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD-1/PD-L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA-seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune-evasive competence.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Leucócitos Mononucleares/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/sangue , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Células Tumorais Cultivadas
6.
Life Sci ; 259: 118193, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32763293

RESUMO

AIMS: Circulating long non-coding RNAs (lncRNAs) have proven to be useful non-invasive tools for diagnosis of various cancers. FAM83H antisense RNA 1 (FAM83H-AS1) and lncRNA activated by TGF ß (lncRNA-ATB) are two lncRNAs that have been shown to play an important role in different cancer types including breast cancer. The primary aim of our study was to investigate the potential role of serum FAM83H-AS1 and lncRNA-ATB as diagnostic/prognostic markers for breast cancer patients. MAIN METHODS: Serum expression levels of FAM83H-AS1 and lncRNA-ATB were analyzed in 90 breast cancer patients and 30 age- and sex-matched healthy controls using RT-qPCR. KEY FINDINGS: We found that FAM83H-AS1 and lncRNA-ATB were significantly overexpressed in sera of breast cancer patients compared to controls (p = 0.000 for both). Analysis of receiver operating characteristic curve demonstrated that lncRNA-ATB had a higher area under curve (AUC) value than the conventional tumor marker cancer antigen 15-3 (CA15-3) (AUC: 0.844, p = 0.000 versus 0.738, p = 0.002) for early diagnosis of breast cancer in patients with stage I-II. On the other hand, FAM83H-AS1 showed a significant correlation with tumor-node metastasis (TNM) stages, large tumor size and lymph node metastasis, suggesting a prognostic rather than diagnostic value. SIGNIFICANCE: This is the first study to demonstrate that serum lncRNA-ATB could be used as a non-invasive diagnostic marker for early stages of breast cancer. Furthermore, serum FAM83H-AS1 has a potential ability for monitoring of progression and staging of breast cancer.


Assuntos
Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Proteínas/análise , RNA Longo não Codificante/sangue , Adulto , Idoso , Diagnóstico Precoce , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Mucina-1/sangue , Valor Preditivo dos Testes , Prognóstico , RNA Antissenso , Curva ROC , Fator de Crescimento Transformador beta
7.
Support Care Cancer ; 28(11): 5085-5097, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32621264

RESUMO

BACKGROUND: PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted in its increased use by physicians; however, the superiority of PEGylated G-CSF for CIN in breast cancer has not been conclusively determined. OBJECTIVES: To assess the superiority of PEGylated G-CSF for CIN in breast cancer in terms of effectiveness and safety via a systematic review and meta-analysis. METHODS: A literature search in PubMed, Embase, Cochrane Library, and Web of Science was performed for eligible studies published from database inception to December 2019. All studies comparing PEGylated G-CSF and G-CSF for CIN of breast cancer were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently. Meta-analysis was conducted using Revman, version 5.2. RESULTS: Nine randomized controlled trials were finally identified. The publication bias of these studies was acceptable. For the endpoint of effectiveness, analysis of the incidence/duration of grade ≥ 3 neutropenia, the duration of grade 4 neutropenia, the incidence of febrile neutropenia (FN), and the time to absolute neutrophil count recovery showed no advantage of PEGylated G-CSF over G-CSF for CIN of breast cancer (P > 0.05), with the premise of a sufficient dose of G-CSF according to the guidelines. No significant differences in grade 4 adverse events were observed between the groups (P = 0.29), and PEGylated G-CSF did not increase the incidence of skeletal and/or muscle pain compared with G-CSF (P = 0.32). CONCLUSION: PEGylated G-CSF was as effective and safe as G-CSF to reduce CIN in breast cancer but did not show an obvious superiority. However, in clinical practice, PEGylated G-CSF has an obvious advantage in terms of convenience, which could improve patient's quality of life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutropenia/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Feminino , Humanos , Neutropenia/induzido quimicamente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem
8.
J Steroid Biochem Mol Biol ; 202: 105726, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682059

RESUMO

Recent evidences suggest a protective mechanism of vitamin D signaling against breast cancer by the autocrine/paracrine manner and may modestly reduce the risk of breast cancer. Despite lots of sunshine, vitamin D deficiency is widespread in India. Moreover, there are limited studies from Indian population regarding circulatory 25(OH) D and breast cancer risk. Thus, the aim of the present study is to investigate circulatory 25(OH) D in relation to breast cancer risk and its association with various clinico-pathological parameters from Indian population. Total 297 subjects, comprising of 157 controls and 140 breast cancer patients were enrolled for the study. Circulatory 25(OH) D was analyzed by HPLC. Statistical analysis was carried out by SPSS software version 15. Further, subjects were categorized into severe, moderate, mild vitamin D deficiency and sufficiency. The prevalence of severe and moderate 25(OH) D deficiency was higher in breast cancer patients as compared to controls. Mean values of 25(OH) D were lower in breast cancer patients as compared to controls in mild, moderate and severe deficient groups (p = 0.07, p = 0.003 and p = 0.001). Moreover, 25(OH) D was significantly lower in postmenopausal breast cancer patients as compared to premenopausal breast cancer patients, particularly in severe deficient group. The levels of 25(OH) D were lower in ER and PR negative receptor status as compared to the positive receptor in severe deficient category (p = 0.06 and p = 0.09 respectively). Whereas, the mean values of 25(OH) D were lower in HER 2 negative receptor status as compared to positive receptor status in the moderate deficient category (p = 0.09). Further, severe deficient group showed significantly lower levels of 25(OH) Din TNBC as compared to luminal A subtype (p = 0.01). Thus, Results indicate that 25(OH) D deficiency might be associated with increased risk of breast cancer. Moreover, severe 25(OH) D deficiency is associated with aggressive behavior of breast cancer.


Assuntos
Neoplasias da Mama/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Prevalência , Receptor ErbB-2 , Receptores Estrogênicos , Receptores de Progesterona , Fatores de Risco , Índice de Gravidade de Doença , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/patologia , Adulto Jovem
9.
Rev Assoc Med Bras (1992) ; 66(5): 673-679, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638964

RESUMO

OBJECTIVE Analyze the over expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) deregulated associated with a poor prognosis in various carcinomas. Our objective was to investigate the relationship between the levels of NEDD-9, CA 15-3, and CEA and PET (SUVmax, MTV40, TLG40) with the clinical parameters of patients with breast cancer (BC). METHODS One hundred and eleven patients (82 BC patients who underwent 18F-FDG PET/CT and 29 healthy controls) were evaluated. SUVmax, MTV, and TLG of the primary tumor were compared with the molecular and histopathological subtypes. 18F-FDG, MTV, and TLG were evaluated based on the clinical data, i.e., nodal involvement, distant metastasis, ER and PR status, Ki-67, serum levels of NEDD-9, CA15-3, and CEA. We compared the NEDD-9 in the BC and healthy control groups. RESULTS The mean ± SD of SUVmax in the 82 patients was 13.0 ± 8.6. A statistically significant relationship (p = 0.022) was found between the molecular subtypes and 18F-FDG uptake. The relationship between 18F-FDG uptake and TLG measured in patients <50 years, ER-PR negativity, and HER2 positivity were statistically significant (p=0.015, 0.007, 0.046, and 0.001, respectively). MTV40, TLG40, and CA 15-3 in metastatic patients were statistically significant (p=0.004, 0.005, and 0.003, respectively). NEDD-9 in the BC group was significantly higher than in the healthy group (p=0.017). There was a positive correlation between SUVmax and Ki67 and CA 15-3; MTV40 and CEA; CA 15-3, CEA, SUVmax, and MTV40; a negative correlation was found between CEA, TLG40, and age. CONCLUSION The use of SUVmax, MTV40, and TLG40 parameters with NEDD-9 and tumor markers has been shown to provide a high diagnostic, predictive, and prognostic value for the management of BC. This is considered to be the basis of interventions focused on the treatment objectives related to NEDD-9.


Assuntos
Neoplasias da Mama/sangue , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Antígeno Carcinoembrionário/sangue , Fluordesoxiglucose F18 , Humanos , Proteínas Associadas aos Microtúbulos/sangue , Mucina-1/sangue , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Anticancer Res ; 40(7): 4147-4156, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620664

RESUMO

BACKGROUND/AIM: We investigated the efficacy of neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and C-reactive protein (CRP) in predicting overall survival of metastatic breast cancer patients treated with eribulin. PATIENTS AND METHODS: Overall, 74 patients treated with eribulin were enrolled and their baseline levels of NLR, ALC, and CRP retrieved. Cutoff values of NLR, ALC, and CRP were set at 3.0, 1500/µl, and 0.3 mg/dl, respectively. Overall survival (OS) was compared according to marker levels. RESULTS: The OS of NLR-low, ALC-high, and CRP-low groups at baseline was significantly longer than that of NLR-high, ALC-low, and CRP-high groups (p=0.0027, p=0.0013, and p=0.0164, respectively). The combination of ALC and CRP was significantly associated with OS by multivariate analysis (p=0.048). CONCLUSION: Baseline levels of NLR, ALC, and CRP were significantly associated with OS in patients treated with eribulin. The combination of ALC and CRP improved the predictive efficacy compared to individual markers.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Furanos/uso terapêutico , Cetonas/uso terapêutico , Linfócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proteína C-Reativa/análise , Feminino , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade
11.
Anticancer Res ; 40(7): 3947-3952, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620636

RESUMO

AIM: This study aimed to evaluate plateletcrit (PCT) and platelet distribution width-to-PCT ratio (PDW/PCT) as potential prognostic biomarkers in patients with breast cancer. PATIENTS AND METHODS: Information of 337 patients was retrospectively reviewed. The Cox regression proportional hazards model was used to evaluate the prognostic value of PCT and PDW/PCT compared to the platelet distribution width-to-platelet count ratio (PDW/P) and red cell distribution width-to-platelet count ratio (RDW/P). RESULTS: Large tumor size (p<0.01), lymph node involvement, and increased PDW/P, RDW/P, and PDW/PCT (p<0.05) were significantly associated with inferior disease-free survival (DFS) according to the univariate analysis. The multivariate analysis showed that large tumor size (p<0.01) and increased PDW/PCT (p<0.05) were significant prognostic factors for poor DFS. CONCLUSION: To our knowledge, this is the first report to show that PDW/PCT is a significant prognostic factor for patients with breast cancer. Therefore, it might be an attractive biomarker providing additional prognostic information for these patients.


Assuntos
Plaquetas/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
12.
Medicine (Baltimore) ; 99(29): e21231, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702897

RESUMO

BACKGROUND: The tumor abnormal protein (TAP) test is used to screen for many cancers, but its use for breast cancer has not been studied. METHODS: Tests for carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and TAP were administered to 261 women with operable benign breast disease and 348 with breast cancer. The cutoff value used for TAP was the mean + 3 standard deviations for benign breast disease patients (275.64 µm). Sensitivities and specificities of single biomarker tests and combined tests were compared. The combined tests were defined as positive if any single biomarker was positive, and negative otherwise. RESULTS: The single biomarker test sensitivities were similar: CEA, 7.18%; CA125, 4.89%; CA15-3, 7.47%; and TAP, 4.89%. For the combinations TAP + CEA + CA125, TAP + CEA + CA15-3, TAP + CA125 + CA15-3, and TAP + CEA + CA125 + CA15-3, the sensitivities were 16.67%, 17.82%, 16.38%, and 21.84%, respectively, and the specificities were 93.49%, 97.70%, 93.87%, and 92.72%. CONCLUSIONS: The 4-test combination showed the highest sensitivity (21.84%) and may be auxiliary used in early screening. TAP + CEA + CA15-3 showed high specificity (97.70%) and so could be used for confirming breast cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Antígeno Ca-125/sangue , Antígeno Carcinoembrionário/sangue , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Mucina-1/sangue , Proteínas de Neoplasias/sangue , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem
13.
Rev Assoc Med Bras (1992) ; 66(6): 732-736, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32696863

RESUMO

OBJECTIVE A previous study has reported that miR-1204 exerted oncogenic effects in breast cancer (BC). The purpose of our paper was to evaluate the expressions of tissue and serum miR-1204 in patients with BC and further investigate its biomarker potential. METHODS The expressions of tissue and serum miR-1204 were investigated by qRT-PCR in 144 BC patients and 38 healthy controls. Chi-square tests were conducted to examine the associations between miR-1204 expressions and clinicopathological factors. Then, the associations of miR-1204s level with the survival of BC patients were determined by performing the Kaplan-Meier and multivariate analysis. The receiver operating characteristics (ROC) and area under the OC curve (AUC) were obtained to validate the diagnostic values of miR-1204. RESULTS We found that the expressions of miR-1204 were increased in both tissue and serum samples from BC patients. Multivariate assays identified tissue and serum miR-1204 overexpression as an independent poor prognostic factor. In addition, ROC curve assays indicated that tissue and serum miR-1204 are potential diagnostic markers of BC. CONCLUSIONS Detection of tissue and serum miR-1204 levels could have clinical potential as a novel prognostic/diagnostic biomarker for BC patients.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , MicroRNAs/sangue , Área Sob a Curva , Neoplasias da Mama/sangue , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Curva ROC
14.
Medicine (Baltimore) ; 99(26): e20681, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590741

RESUMO

Plasma albumin to fibrinogen ratio is involved in human cancer, but its prognostic significance in breast cancer is controversy. In the context of breast invasive ductal carcinoma, this research aims to retrospectively evaluate by preoperative plasma albumin to fibrinogen ratio (AFR) and forecast oncological outcome and recurrence.This retrospective study comprised 230 patients with non-metastatic breast invasive ductal carcinoma who underwent surgery between January 2009 and April 2012 in Fourth Hospital of Hebei Medical University. Patients were categorized base on an optimal value of preoperative plasma fibrinogen (Fib) and albumin. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between albumin to fibrinogen ratio and clinical outcomes were assessed with univariate and multivariate analysis. A number of risk factors were used to form nomograms to evaluate survival, and Harrell concordance index (C-index) was used to evaluate the predictive accuracy.Plasma AFR was significantly associated with diminished disease-free survival (DFS) and overall survival (OS). Multivariate analysis revealed that plasma AFR was an independent prognostic indicator for DFS (HR = 1.346; 95% CI: 1.107-1.636; P = .03) and overall survival (OS) (HR = 1.485; 95% CI: 1.106-1.993; P = .008). Two prediction model of 3-, 5-years OS and DFS based on the AFR was developed.Elevated preoperative plasma AFR is an independent prognostic factor for oncological outcomes in patients with breast invasive ductal carcinoma. The formulated nomogram showed superior predictive accuracy for DFS and OS.


Assuntos
Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Fibrinogênio/análise , Nomogramas , Albumina Sérica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
15.
PLoS One ; 15(6): e0233713, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497068

RESUMO

BACKGROUND: Peripheral blood transcriptome profiling is a potentially important tool for disease detection. We utilize this technique in a case-control study to identify candidate transcriptomic biomarkers able to differentiate women with breast lesions from normal controls. METHODS: Whole blood samples were collected from 50 women with high-risk breast lesions, 57 with breast cancers and 44 controls (151 samples). Blood gene expression profiling was carried out using microarray hybridization. We identified blood gene expression signatures using AdaBoost, and constructed a predictive model differentiating breast lesions from controls. Model performance was then characterized by AUC sensitivity, specificity and accuracy. Biomarker biological processes and functions were analyzed for clues to the pathogenesis of breast lesions. RESULTS: Ten gene biomarkers were identified (YWHAQ, BCLAF1, WSB1, PBX2, DDIT4, LUC7L3, FKBP1A, APP, HERC2P2, FAM126B). A ten-gene panel predictive model showed discriminatory power in the test set (sensitivity: 100%, specificity: 84.2%, accuracy: 93.5%, AUC: 0.99). These biomarkers were involved in apoptosis, TGF-beta signaling, adaptive immune system regulation, gene transcription and post-transcriptional protein modification. CONCLUSION: A promising method for the detection of breast lesions is reported. This study also sheds light on breast cancer/immune system interactions, providing clues to new targets for breast cancer immune therapy.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Detecção Precoce de Câncer/métodos , Modelos Genéticos , Transcriptoma , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Confiabilidade dos Dados , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
16.
Medicine (Baltimore) ; 99(22): e20346, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481414

RESUMO

The immune system plays a fundamental role in the response to neoadjuvant chemotherapy (NAC) of locally advanced breast cancer (LABC) patients. Patients with pathological complete response (pCR) after NAC have a higher survival rate. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral blood indicators of inflammatory response. This investigates the correlation between NLR, PLR, LMR, and other clinicopathological features of breast cancer patients before receiving NAC and pCR.Data of LABC patients who underwent NAC between 2009 and 2018 were retrospectively reviewed. Each patient's peripheral complete blood count was recorded before starting NAC. The cut-off values for neutrophils, lymphocytes, monocytes, and platelets in the peripheral blood and NLR, PLR, and LMR were determined by receiver operating characteristic curve analyses.The records of 131 patients were analyzed and divided into two groups, pCR (+ve) and pCR (-ve), and their clinicopathological features and laboratory findings were compared. pCR was achieved in 23.6% of patients. The cut-off values of neutrophils, lymphocytes, monocytes, and platelets at the time of diagnosis and NLR, PLR, and LMR were, respectively, 4150 µL, 2000 µL, 635 µL, 271 × 10 µL, 1.95, 119, and 3.35. The pCR rate was higher in patients with low neutrophil count, low NLR, and high lymphocyte count (P = .002, <.001, and .040, respectively).As per the findings of multivariate logistic regression analysis, the independent predictive factors of pCR were clinical tumor size T1 and T2, grade 3, ER negativity, and low NLR (P = .015, .001, .020, .022, and .001, respectively).While NLR was found to be an independent predictive factor of pCR in LABC patients receiving NAC, a similar result was not observed for PLR and LMR. NLR can be a useful biomarker for predicting the response of patients receiving NAC.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Mediadores da Inflamação/sangue , Adulto , Idoso , Biomarcadores Tumorais , Plaquetas/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
17.
Oncology ; 98(10): 714-718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32516768

RESUMO

BACKGROUND: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. METHODS: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. RESULTS: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5-43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0-108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4-10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9-30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. CONCLUSION: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Antígeno Carcinoembrionário/sangue , Feminino , Fluordesoxiglucose F18 , Humanos , Mucina-1/sangue , Metástase Neoplásica , Recidiva Local de Neoplasia/sangue , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos
18.
Breast Cancer Res ; 22(1): 56, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32466779

RESUMO

BACKGROUND: Endocrine therapy is recommended as a first-line treatment for hormone receptor-positive metastatic breast cancer (HR+MBC) patients. No biomarker has been validated to predict tumor progression in that setting. We aimed to prospectively compare the risk of early progression according to circulating ESR1 mutations, CA-15.3, and circulating cell-free DNA in MBC patients treated with a first-line aromatase inhibitor (AI). METHODS: Patients with MBC treated with a first-line AI were prospectively included. Circulating biomarker assessment was performed every 3 months. The primary objective was to determine the risk of progression or death at the next follow-up visit (after 3 months) in case of circulating ESR1 mutation detection among patients treated with a first-line AI for HR+MBC. RESULTS: Overall, 103 patients were included, and 70 (68%) had progressive disease (PD). Circulating ESR1 mutations were detected in 22/70 patients with PD and in 0/33 patients without progression (p < 0.001). Among the ESR1-mutated patients, 18/22 had a detectable mutation prior to progression, with a median delay of 110 days from first detection to PD. The detection of circulating ESR1 mutations was associated with a 4.9-fold (95% CI 3.0-8.0) increase in the risk of PD at 3 months. Using a threshold value of 25% or 100%, a CA-15.3 increase was also correlated with progression (p < 0.001 and p = 0.003, respectively). In contrast to ESR1, the CA-15.3 increase occurred concomitantly with PD in most cases, in 27/47 (57%) with a 25% threshold and in 21/25 (84%) with a 100% threshold. Using a threshold value of either 25% or 100%, cfDNA increase was not correlated with progression. CONCLUSION: The emergence of circulating ESR1 mutations is associated with a 4.9-fold increase in the risk of early PD during AI treatment in HR+MBC. Our results also highlighted that tracking circulating ESR1 mutations is more relevant than tracking CA-15.3 or cfDNA increase to predict progression in this setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02473120. Registered 16 June 2015-retrospectively registered after one inclusion (first inclusion 1 June 2015).


Assuntos
Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , DNA Tumoral Circulante/sangue , Receptor alfa de Estrogênio/genética , Mucina-1/sangue , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , DNA Tumoral Circulante/genética , Estudos de Coortes , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Receptor alfa de Estrogênio/sangue , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
19.
Medicine (Baltimore) ; 99(20): e20231, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443355

RESUMO

BACKGROUND: To systematically evaluate the effects of physical activity on physiological markers in breast cancer survivors. METHODS: A systematic search of the PubMed, Wed of Science, Medline, CNKI and Wanfang Database was performed to identify eligible randomized controlled trials to explore physical activity on physiological markers in breast cancer survivors. STATA version 13.0 (Stata Corp LP, College Station, TX) was used for all statistical analyses. RESULTS: A total of 11 articles with 941 cases were eligible in this meta-analysis. The results of the meta-analysis showed that physical activity could decrease the levels of insulin (SMD = -1.90, 95%CI: -3.2 to -0.60; I = 92.3%, P < .001), insulin-like growth factor 1 (IGF-I) (WMD = -4.67, 95%CI: -23.14 to 13.79; I = 96.2%, P < .001), insulin-like growth factor binding protein-3 (IGFBP-3) (WMD = -20.09, 95%CI: -47.15 to 6.97; I = 93.3%, P < .001). However, compared with the control group, there was not the significant change of insulin-like growth factor 2 (IGF-II), insulin-like growth factor binding protein-1 (IGFBP-1), leptin, adiponectin, glucose, C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-ɑ) levels after the intervention. CONCLUSIONS: Physical activity could improve the insulin function that might be associated with decreasing the levels of IGF-I, IGFBP-3 and insulin in breast cancer survivors.


Assuntos
Biomarcadores/análise , Neoplasias da Mama/sangue , Exercício Físico/fisiologia , Adulto , Biomarcadores/sangue , Neoplasias da Mama/fisiopatologia , Sobreviventes de Câncer , Feminino , Humanos , Insulina/análise , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue
20.
Medicine (Baltimore) ; 99(18): e18755, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358341

RESUMO

Many inflammation indicators have been reported to be related with patient outcomes in various cancers. Previous studies have evaluated the combination of platelet (PLT) and lymphocyte to monocyte ratio (COP-LMR) as a systemic inflammatory marker for prognostication in lung cancer, yet its prognostic role among breast cancer patients remains unclear.In the present study, a total of 409 breast cancer patients with surgical resection were retrospectively investigated. The receiver operating characteristic (ROC) curve was used to choose the optimal cut-off value of PLT and lymphocyte to monocyte ratio (LMR). Patients were classified into 3 groups according to the score of COP-LMR, and its relationship with various clinicopathological factors and breast cancer prognosis were further evaluated.The ROC curve analysis showed that COP-LMR had a higher area under the ROC curve for the prediction of 5-year disease-free survival and overall survival than PLT or LMR alone. Multivariable analysis showed that an elevated COP-LMR was an independent predictor of poor disease-free survival (P = .032) and overall survival (P = .005). Subgroup analysis revealed that COP-LMR was still significantly associated with prognosis in both luminal A and luminal B subtypes.Preoperative COP-LMR is a potential prognostic factor in breast cancer patients who underwent surgery.


Assuntos
Neoplasias da Mama/mortalidade , Contagem de Leucócitos/estatística & dados numéricos , Linfócitos , Monócitos , Contagem de Plaquetas/estatística & dados numéricos , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos
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