RESUMO
This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.
Assuntos
Neoplasias da Mama , Chaperonina 60 , Proteínas de Choque Térmico HSP70 , Resistência à Insulina , Pós-Menopausa , Humanos , Feminino , Neoplasias da Mama/sangue , Estudos Transversais , Pós-Menopausa/sangue , Pessoa de Meia-Idade , Proteínas de Choque Térmico HSP70/sangue , Chaperonina 60/sangue , Idoso , Citocinas/sangue , Interleucina-6/sangue , Interleucina-10/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
PURPOSE: Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing. METHODS: We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery. RESULTS: Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371). CONCLUSIONS: Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Neoplasias da Mama , Ácidos Nucleicos Livres , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Projetos Piloto , Adulto , Idoso , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Resultado do Tratamento , Prognóstico , Quimioterapia Adjuvante/métodosRESUMO
BACKGROUND: The human telomerase reverse transcriptase (hTERT) enzyme, encoded by the hTERT gene, synthesizes protective telomeric sequences on chromosomes and plays a fundamental role in cancer formation. Methylation of the hTERT gene has an upregulatory effect, increasing hTERT enzyme synthesis and allowing continuous tumor cell division. OBJECTIVE: In a group of patients with breast cancer, we aimed to analyze the methylation status of hTERT in the tumor, surrounding tissue, and circulating free deoxyribonucleic acid (cfDNA) of blood collected on the day of mastectomy and then approximately one year later. DESIGN AND SETTING: A prospective study was conducted at a university hospital in Rio de Janeiro, Brazil. METHODS: Samples were collected from 15 women with breast cancer on the day of mastectomy and approximately one year postoperatively. cfDNA was analyzed by sodium bisulfite conversion, followed by polymerase chain reaction, electrophoresis, and silver nitrate staining. RESULTS: Methylation of hTERT was detected in the tumors and surrounding tissues of all 15 patients. Five patients displayed hTERT methylation in the cfDNA from the blood of the first collection. Of the ten patients who returned for the second collection, three showed methylation. Two patients with methylation in the first collection did not display methylation in the second collection. One patient with no methylation in the first collection displayed methylation in the second collection, and one patient had a diminished level of methylation in the second collection. CONCLUSION: Only one-third of patients displayed methylation in their cfDNA, which may be related to the success of chemotherapy.
Assuntos
Neoplasias da Mama , Metilação de DNA , Telomerase , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/sangue , Mastectomia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Telomerase/genética , Telomerase/sangueRESUMO
Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.
Assuntos
Neoplasias da Mama , Aprendizado de Máquina , Humanos , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Contagem de Células Sanguíneas/métodos , Medição de Risco/métodos , Detecção Precoce de Câncer/métodos , Brasil/epidemiologiaRESUMO
Breast cancer is one of the most prevalent malignancies affecting women globally and poses a significant public health challenge. Early clinical detection plays a pivotal role in providing optimal treatment opportunities and favorable prognoses, crucial for reducing breast cancer mortality and enhancing patients' quality of life. Therefore, the timely identification and diagnosis of breast cancer are imperative. Conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3), serve as reliable methods for actively monitoring disease progression and have become a routine auxiliary diagnostic approach in clinical settings. However, these biomarkers exhibit limitations in sensitivity and specificity, particularly in the early screening and diagnosis of tumors, often yielding results inconsistent with clinical manifestations. In recent years, research has increasingly focused on exosomes released by tumor cells as potential new biomarkers for early stage breast cancer screening. Exosomes carry various components, including tumor-derived proteins, nucleic acids, and lipids. This paper delves into the specific utilization of serum exosomal microRNA-21 (miR-21) as a biomarker for early detection and diagnosis of breast cancer, evaluating its efficacy within this framework.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Detecção Precoce de Câncer , Exossomos , MicroRNAs , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Feminino , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodosRESUMO
PURPOSE: Systemic immune-inflammatory markers have a certain predictive role in pathological complete response (pCR) after neoadjuvant treatment (NAT) in breast cancer. However, there is a lack of research exploring the predictive value of markers after treatment. METHODS: This retrospective study collected data from 1994 breast cancer patients who underwent NAT. Relevant clinical and pathological characteristics were included, and pre- and post-treatment complete blood cell counts were evaluated to calculate four systemic immune-inflammatory markers: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). The optimal cutoff values for these markers were determined using ROC curves, and patients were classified into high-value and low-value groups based on these cutoff values. Univariate and multivariate logistic regression analyses were conducted to analyze factors influencing pCR. The factors with independent predictive value were used to construct a nomogram. RESULTS: After NAT, 383 (19.2%) patients achieved pCR. The area under the ROC curve is generally larger for post-treatment markers compared to pre-treatment markers. Pre-treatment NLR and PLR, as well as post-treatment LMR and SII, were identified as independent predictive factors for pCR, along with Ki-67, clinical tumor stage, clinical lymph node stage, molecular subtype, and clinical response. Higher pre-NLR (OR = 1.320; 95% CI 1.016-1.716; P = 0.038), pre-PLR (OR = 1.474; 95% CI 1.058-2.052; P = 0.022), post-LMR (OR = 1.532; 95% CI 1.175-1.996; P = 0.002), and lower post-SII (OR = 0.596; 95% CI 0.429-0.827; P = 0.002) are associated with a higher likelihood of achieving pCR. The established nomogram had a good predictive performance with an area under the ROC curve of 0.754 (95% CI 0.674-0.835). CONCLUSION: Both pre- and post-treatment systemic immune-inflammatory markers have a significant predictive role in achieving pCR after NAT in breast cancer patients. Indeed, it is possible that post-treatment markers have stronger predictive ability compared to pre-treatment markers.
Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Neutrófilos , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Curva ROC , Biomarcadores Tumorais/sangue , Linfócitos , Idoso , Inflamação/sangue , Valor Preditivo dos Testes , Nomogramas , Plaquetas/patologia , Monócitos , PrognósticoRESUMO
Breast cancer is a multifactorial disease in which the interplay among multiple risk factors remains unclear. Energy homeostasis genes play an important role in carcinogenesis and their interactions with the serum concentrations of IGF-1 and IGFBP-3 on the risk of breast cancer have not yet been investigated. The aim of this study was to assess the modifying effect of the genetic variation in some energy homeostasis genes on the association of serum concentrations of IGF-1 and IGFBP-3 with breast cancer risk. We analyzed 78 SNPs from 10 energy homeostasis genes in premenopausal women from the 4-Corner's Breast Cancer Study (61 cases and 155 controls) and the Mexico Breast Cancer Study (204 cases and 282 controls). After data harmonization, 71 SNPs in HWE were included for interaction analysis. Two SNPs in two genes (MBOAT rs13272159 and NPY rs16131) showed an effect modification on the association between IGF-1 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). In addition, five SNPs in three genes (ADIPOQ rs182052, rs822391 and rs7649121, CARTPT rs3846659, and LEPR rs12059300) had an effect modification on the association between IGFBP-3 serum concentration and breast cancer risk (Pinteraction < 0.05, adjusted Pinteraction < 0.20). Our findings showed that variants of energy homeostasis genes modified the association between the IGF-1 or IGFBP-3 serum concentration and breast cancer risk in premenopausal women. These findings contribute to a better understanding of this multifactorial pathology.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Metabolismo Energético/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pré-Menopausa , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
Breast cancer (Bca) is the most common type of cancer among women worldwide, and oxidative stress caused by adjuvant treatment may be decreased by antioxidant intake. The aim of this study is to investigate the associations between Dietary antioxidant Capacity (DaC) and oxidation and antioxidant biomarkers in women undergoing adjuvant treatment (AT) for Bca. This prospective study had a sample of 70 women (52.2 ± 10.7 y). DaC (mmol/g) was calculated using nutritional data obtained from a Food Frequency Questionnaire, and blood was collected to measure the oxidation and antioxidant biomarkers at baseline (T0), and after AT (T1). Carbonylated protein levels were inversely associated with DaC at T1 (p = 0.004); women showed an increased risk of having increment on lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and decrement on ferric reducing antioxidant power (FRAP) and reduced glutathione after AT, in response to lowered DaC (p < 0.05). Carbonylated proteins, TBARS and FRAP levels remained stable between the periods for women at the 3rd DaC tertile at T1, differentiating them from those at the 1st tertile, who showed negative changes in these biomarkers (p < 0.04). DaC may be beneficial for women undergoing AT for Bca, since it promoted a reduction in oxidative stress.
Assuntos
Antioxidantes/administração & dosagem , Neoplasias da Mama/sangue , Dieta/métodos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Biomarcadores/sangue , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/efeitos adversos , Inquéritos sobre Dietas , Ingestão de Alimentos/fisiologia , Feminino , Glutationa/sangue , Humanos , Peróxidos Lipídicos/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Carbonilação Proteica/efeitos dos fármacos , Radioterapia Adjuvante/efeitos adversos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
BACKGROUND: While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density. METHODS: A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers' Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors. RESULTS: Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components. CONCLUSIONS: We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.
Assuntos
Biomarcadores/sangue , Densidade da Mama/fisiologia , Pré-Menopausa , Adulto , Índice de Massa Corporal , Mama/diagnóstico por imagem , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Mamografia , Metabolômica , México , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Fatores de Risco , Esfingomielinas/sangueRESUMO
Adenine nucleotides are important signaling molecules that mediate biological functions in many conditions, including cancer. The enzymes CD39 and CD73 produce adenosine in the extracellular milieu that has a very important role in tumor development. This study aimed to evaluate nucleotide hydrolysis in the plasma blood of breast cancer elderly patients. In this prospective cohort study, we investigated the ectonucleotidases activity in breast cancer elderly patients, at the moment of diagnosis and after treatment. Control group consisted of elderly women without cancer diagnostic. The nucleotide hydrolysis assay was performed by the malachite green method and used ATP, ADP, or AMP as substrates. Paired t test or Wilcoxon rank-sum test was used. Our data showed that breast cancer patients presented high levels of ATP and AMP hydrolyses when compared to control group at the moment of diagnosis. When analyzing the differences between the samples at the time of diagnostic and 6 months after treatment, we observed a significant reduction on CD73 activity after all treatments used: surgery, chemotherapy, radiotherapy, or hormone therapy. The results with APCP, a specific CD73 inhibitor, showed that the AMP hydrolysis was inhibited in all conditions evaluated. We observed a diminished ADPase activity in the patients without metastasis when compared to metastatic breast cancer patients. The results showed that AMP hydrolysis was reduced in the blood plasma of breast cancer elderly patients after different treatments. This study strengthens the potential role of CD73 enzyme as a biomarker for breast cancer treatment response.