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Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity. Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA, AKT1, ESR1, ERBB2, BRCA1, BRCA2, PALB2, TP53, but not PTEN) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]). Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1. Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2, or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases. Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives.
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Liquid biopsy is increasingly vital in monitoring neoadjuvant breast cancer treatment. This study collected plasma samples at three time points from participants in the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE), analyzing miRNA expression with NanoString's nCounter® Human v3 miRNA assay. In the carboplatin arm, four ct-miRNAs exhibited dynamic changes linked to pathologic complete response, with a combined area under the curve of 0.811. Similarly, the non-carboplatin arm featured four ct-miRNAs with an area under the curve of 0.843. These findings underscore the potential of ct-miRNAs as personalized tools in breast cancer treatment, assisting in predicting treatment response and assessing the risk of relapse. Integrating ct-miRNA analysis into clinical practice can optimize decisions and enhance patient outcomes.
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MicroRNA Circulante , MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Carboplatina/uso terapêutico , Pesquisa Translacional Biomédica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/tratamento farmacológico , MicroRNAs/genética , Biomarcadores , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
This exploratory analysis of the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE) study aimed to identify the biomarkers of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC) within the context of a clinical trial. The NACATRINE trial is a phase II, single-center, randomized, open-label clinical trial that investigated the addition of carboplatin to sequential anthracycline- and taxane-based NAC for TNBC. We evaluated the gene expression in untreated samples to investigate its association with pCR, overall survival (OS), and disease-free survival (DFS). RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel was used to analyze gene expression. Of the 66 patients included in the gene expression profiling analysis, 24 (36.4%) achieved pCR and 42 (63.6%) had residual disease. In unsupervised hierarchical clustering analyses, differentially expressed genes between patients with and without pCR were identified irrespective of the treatment (24 genes), carboplatin (37 genes), and non-carboplatin (27 genes) arms. In receiver operating characteristic (ROC) curve analysis, 10 genes in the carboplatin arm (area under the ROC curve [AUC], 0.936) and three genes in the non-carboplatin arm (AUC, 0.939) were considered to be potential pCR-associated biomarkers. We identified genes that were associated with improvements in OS and DFS in addition to being related to pCR. We successfully identified gene expression signatures associated with pCR in pretreatment samples of patients with TNBC treated with NAC. Further investigation of these biomarkers is warranted.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Carboplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Biomarcadores , Expressão GênicaRESUMO
BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been recently developed and introduced into clinical practice. METHODS: We retrospectively analyzed data from patients with confirmed HR+/HER2 metastatic breast cancer treated with hormonal therapy in combination with ribociclib (R), palbociclib (P), or abemaciclib (A). OUTCOMES: median progression-free survival (mPFS), time to treatment discontinuation (mTTD), and objective response rate (ORR). RESULTS: Between January 2016 - June 2021, 142 patients were treated with an CDK4/6i (79 P, 42 R, 21 A). The median age was 59 years and 67.6% had recurrent disease. Roughly 35.2%, 36.6%, 28.2% of the patients had 1, 2 or 3+ metastatic sites, respectively, and 55.6% of the patients received CDK4/6i as a first-line treatment. The mPFS was 28m(R) vs. 14m(P) vs. 6m(A) (P = 0.002), with a higher proportion of patients receiving R in the first-line setting. However, no difference was seen when the analysis was restricted to the first-line scenario (P = 0.193). Sixty-four patients required one dose reduction, and 19 patients required two. ORR was 76.2% (R) vs 62% (P) vs 42.9% (A). More patients achieved a complete response with R and P, with no difference in the incidence of partial response and stable disease. Adverse events occurred in 94.4% of the population, with the most common grade 3-4 AE being neutropenia (59.1%). CONCLUSIONS: Our results confirm the efficacy and tolerability of CDK4/6i in routine clinical practice. This is the first real-world data describing and comparing the efficacy and toxicity of CDK4/6i in the Brazilian population.
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Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Brasil , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.
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BACKGROUND: Takotsubo syndrome (TTS), also known as stress cardiomyopathy, apical ballooning syndrome and broken heart syndrome, is characterized by acute-onset chest pain, electrocardiographic (ECG) abnormalities and reversible left ventricular (LV) disfunction in the absence of a culprit obstructive lesion in the coronary arteries; therefore, myocardial infarction is the most important differential diagnosis. Usually induced by emotional/physical stress, its treatment consists in hemodynamic support until complete and spontaneous recovery occurs, which is generally achieved within a few days to weeks. Cervical malignancies are an important public health issue in low/middle-income countries and, in the setting of locally advanced disease, concurrent chemoradiation followed by brachytherapy is considered the standard treatment, harboring curative potential. CASE REPORT: We report a case of a 38-year-old woman who underwent concurrent chemoradiotherapy and developed cardiopulmonary arrest in ventricular fibrillation during a brachytherapy session. Complementary tests disclosed altered ECG and cardiac biomarkers, no evidence of coronary artery obstruction, as well as LV disfunction consistent with TTS on echocardiogram and cardiac MRI. After few days of supportive therapy, complete recovery of heart function was observed. CONCLUSIONS: Especially for cancer patients, who usually experience intense emotional/physical stress intrinsically associated with their diagnosis and aggressive treatments, considering TTS as a differential diagnosis is warranted. Intracavitary brachytherapy procedure may represent a trigger for TTS.
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BACKGROUND: Use of mammary adenectomy for breast carcinoma treatment remains controversial. OBJECTIVE: This study aimed to verify the oncological safety of mammary adenectomy and immediate breast reconstruction for treating selected patients with infiltrating breast carcinoma and to evaluate patients' satisfaction with the reconstructed breasts. DESIGN AND SETTING: Cohort study conducted among patients treated at Hospital Sírio-Libanês, São Paulo, Brazil. METHODS: This study was based on 152 selected patients (161 operated breasts) with infiltrating breast carcinoma who underwent mammary adenectomy and immediate breast reconstruction. In all patients, the diameter of the largest focus of the tumor was less than 3.0 cm, the imaging tumor-nipple distance was greater than 2.0 cm and the pathological assessment showed clear margins. The cumulative incidence of local recurrence (LR), recurrence-free survival (RFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. After at least one year of follow-up, 64 patients were asked about their satisfaction with the reconstructed breast(s). RESULTS: At a mean follow-up time of 43.5 months, seven cases of LR (4.4%), four distant metastases (2.6%) and five deaths (3.3%) were recorded. The five-year actuarial LR-free survival, RFS and OS were 97.6%, 98.3% and 98.3%, respectively. No cases of nipple-areolar complex recurrence were reported. Forty-one patients (64%) indicated a high level of satisfaction with the reconstructed breasts. CONCLUSIONS: Mammary adenectomy is a safe and efficacious procedure for selected patients with early-infiltrating breast carcinoma and results in a high rate of patient satisfaction with the reconstructed breasts.
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Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Mamoplastia/métodos , Satisfação do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Mastectomia/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
ABSTRACT BACKGROUND: Use of mammary adenectomy for breast carcinoma treatment remains controversial. OBJECTIVE: This study aimed to verify the oncological safety of mammary adenectomy and immediate breast reconstruction for treating selected patients with infiltrating breast carcinoma and to evaluate patients' satisfaction with the reconstructed breasts. DESIGN AND SETTING: Cohort study conducted among patients treated at Hospital Sírio-Libanês, São Paulo, Brazil. METHODS: This study was based on 152 selected patients (161 operated breasts) with infiltrating breast carcinoma who underwent mammary adenectomy and immediate breast reconstruction. In all patients, the diameter of the largest focus of the tumor was less than 3.0 cm, the imaging tumor-nipple distance was greater than 2.0 cm and the pathological assessment showed clear margins. The cumulative incidence of local recurrence (LR), recurrence-free survival (RFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. After at least one year of follow-up, 64 patients were asked about their satisfaction with the reconstructed breast(s). RESULTS: At a mean follow-up time of 43.5 months, seven cases of LR (4.4%), four distant metastases (2.6%) and five deaths (3.3%) were recorded. The five-year actuarial LR-free survival, RFS and OS were 97.6%, 98.3% and 98.3%, respectively. No cases of nipple-areolar complex recurrence were reported. Forty-one patients (64%) indicated a high level of satisfaction with the reconstructed breasts. CONCLUSIONS: Mammary adenectomy is a safe and efficacious procedure for selected patients with early-infiltrating breast carcinoma and results in a high rate of patient satisfaction with the reconstructed breasts.
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Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Satisfação do Paciente , Mamoplastia/métodos , Carcinoma Ductal de Mama/cirurgia , Estudos Retrospectivos , Estudos de Coortes , Seguimentos , Resultado do Tratamento , Intervalo Livre de Doença , Mastectomia/métodos , Recidiva Local de NeoplasiaRESUMO
OBJECTIVE: Metastases are rare in early breast cancer (EBC), and international guidelines recommend against routine systemic staging for asymptomatic patients. However, imaging exams remain widely employed in the clinical practice. The aim of the present study is to evaluate the value of imaging for systemic staging in EBC. METHODS: A retrospective analysis of newly-diagnosed breast cancer (BC) patients was performed. Clinical data including BC subtype, stage, presence of symptoms at diagnosis and instrumental procedures performed for staging were recorded. RESULTS: A total of 753 patients were included, with a median age of 57 years. The majority of the patients underwent at least 1 imaging procedure (91%); had invasive ductal carcinoma (83.5%); histological grade 2 (51.4%); stage II (61.8%); and luminal subtype (67.9%). Among the 685 (91%) patients who underwent any radiologic staging, distant metastases (DMs) were detected in 32 (4.7%). In the univariate analyses, stage IIb and pathological lymph node involvement (pN1) showed a statistically significant association with the presence of DMs, versus only a trend for triple negative and human epidermal growth factor receptor 2 (Her2) positive subtype. In an exploratory analysis performed in this same subgroup, when unfavorable biology (triple negative or Her2 positive) was present, patients had a DM rate of 14.4%, one of the highest reported at this stage of the disease. CONCLUSION: Early breast cancer has a low prevalence of DM at the initial evaluation, and systemic staging of asymptomatic, unselected patients is not warranted as a routine practice. However, we have identified subgroups of patients to whom a full staging could be indicated.
OBJETIVO: Metástases são de ocorrência rara no câncer de mama precoce, e as diretrizes internacionais não recomendam o estadiamento sistêmico de rotina para pacientes assintomáticos. Apesar disso, exames de imagem continuam sendo largamente empregados na prática clínica. O objetivo do presente estudo é avaliar o valor do estadiamento por imagem no câncer de mama precoce. MéTODOS: Análise retrospectiva de pacientes recém-diagnosticados com câncer de mama. Foram registrados os dados clínicos dos pacientes, incluindo subtipo da neoplasia de mama, estadiamento, presença de sintomas no momento do diagnóstico e procedimentos de estadiamento. RESULTADOS: Um total de 753 pacientes foram incluídos, com idade média de 57 anos. Grande parte deles se submeteu a pelo menos um exame de imagem (91%); tinha carcinoma ductal invasivo (83,5%); grau histológico 2 (51,4%); estádio II (61,8%); e subtipo luminal (67,9%). Entre os 685 (91%) pacientes que realizaram algum exame de imagem, metástases à distância foram detectadas em 32 (4,7%). Na análise univariada, estádio IIb e acometimento linfonodal (pN1) tiveram uma associação estatisticamente significativa com a presença de metástase, enquanto os subtipos triplo negativo e receptor tipo 2 do fator de crescimento epidérmico humano (Her2) positivo demonstraram apenas uma tendência para a identificação de metástases. Na análise exploratória deste mesmo subgrupo, diante da presença de biologia desfavorável (triplo negativo e Her2 positivo), os pacientes apresentaram uma taxa de metástase à distância de 14,4%, uma das mais altas relatadas nesse estádio. CONCLUSãO: Neoplasia de mama precoce apresenta baixa baixa prevalência de metástase à distância no momento do diagnóstico, e o estadiamento sistêmico de rotina de pacientes assintomáticos e não selecionados não é justificável. Contudo, identificamos subgrupos de pacientes para os quais o estadiamento completo poderia ser indicado.
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Doenças Assintomáticas , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).
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Antagonistas Adrenérgicos beta/uso terapêutico , Antineoplásicos/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/prevenção & controle , Carvedilol/uso terapêutico , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE/OBJECTIVE(S): Skin sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have entered routine surgical practice for breast cancer, though their oncologic safety has not been established in randomized controlled trials. The aim of this study was to evaluate and compare radiation oncologists' and breast surgeons' opinions concerning the indications of post-operative radiation therapy (PORT) after SSM and NSM. MATERIALS/METHODS: Radiation oncologists and breast surgeons from North America, South America and Europe were invited to contribute in this study. A 22-question survey was used to evaluate their opinions. RESULTS: A total of 550 physicians (298 radiation oncologists and 252 breast surgeons) answered the survey. The majority of responders affirmed that PORT should be performed in early-stage (stages I and II) breast cancer for patients who present with risk factors for relapse after SSM and NSM. They considered age, lymph node involvement, tumor size, extracapsular extension, involved surgical margins, lymphovascular invasion, triple negative receptor status and multicentric presentation as major risk factors. Considering that after SSM and NSM, residual breast tissue can be left behind, the residual tissue considered as acceptable in the context of an oncologic surgery were 1-5 mm for breast surgeons. There is no consensus for the necessity of evaluating residual breast tissue through breast imaging. CONCLUSION: Although the indications of PORT after SSM and NSM vary among practitioners, standard risk factors for relapse are considered as important by radiation oncologists and breast surgeons.
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Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Padrões de Prática Médica/estatística & dados numéricos , Terapia Combinada , Europa (Continente) , Feminino , Humanos , Recidiva Local de Neoplasia , Mamilos , América do Norte , América do Sul , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: This study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site. MATERIAL AND METHODS: Between 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation. RESULTS: 2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 ± 2.4 months and 45.1 ± 2.9 months, respectively. Three- and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001). CONCLUSION: RT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1-3 metastatic sites), and the use of hormone therapy.
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Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/radioterapia , Carcinoma Lobular/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Uterine carcinosarcoma is well known for its aggressive behavior. There is little evidence regarding the gold standard combination chemotherapy in metastatic or locally advanced carcinosarcoma, due to poor survival outcomes obtained with conventional scheduled chemotherapy. This case report represents the first-ever reported objective response to a metronomic chemotherapy regimen and adds to the current literature. CASE PRESENTATION: We describe a case of a Caucasian woman diagnosed with metastatic carcinosarcoma that had already been treated with multiple lines of conventional chemotherapy, with progressive disease. This patient had a surprising clinical and imaging response when treated with oral metronomic cyclophosphamide. CONCLUSIONS: We reviewed the mechanism of action implicated in metronomic chemotherapy, and correlated it with the biology of disease in carcinosarcoma. This information may add to the current literature, providing important insights to future clinical trials in this patient population.
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Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinossarcoma/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Sarcoma do Estroma Endometrial/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Administração Metronômica , Antineoplásicos Alquilantes/toxicidade , Carcinossarcoma/patologia , Ciclofosfamida/toxicidade , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Peritoneais/secundário , Sarcoma do Estroma Endometrial/patologia , Resultado do Tratamento , Neoplasias Uterinas/psicologiaRESUMO
OBJECTIVE: The selection of breast cancer patients as candidates for nipple-sparing mastectomy (NSM) is dependent on the preoperative detection of neoplastic involvement of the nipple-areola complex (NAC). This cross-sectional study was designed to evaluate the accuracy of preoperative breast MRI as a noninvasive method to predict neoplastic involvement of the nipple. MATERIALS AND METHODS: We included 165 female breast cancer patients with a surgical plan that included total mastectomy or breast conservation surgery with the removal of the NAC. All patients underwent MRI before surgery on a 1.5-T unit with a 4-channel in vivo dedicated surface breast coil. One radiologist who was blinded to the results of the histologic evaluations of the specimens evaluated the MRI studies. RESULTS: Of the 170 mastectomy specimens evaluated, 37 (21.8%) had neoplastic involvement of the NAC. The MRI findings of enhancement between the index lesion and the NAC and of nipple retraction were considered statistically significant predictors of nipple involvement in breast cancer patients (p < 0.01 and p = 0.01, respectively). The negative predictive value of the combination of these MRI findings was 83.3%. CONCLUSION: Breast MRI is a safe noninvasive method to preoperatively evaluate breast cancer patients eligible for NSM with a high specificity and a high negative predictive value when enhancement between the index lesion and the nipple and nipple retraction are analyzed.
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Neoplasias da Mama/patologia , Imageamento por Ressonância Magnética , Mamilos/patologia , Neoplasias da Mama/cirurgia , Estudos Transversais , Feminino , Humanos , Mastectomia Segmentar , Mastectomia Simples , Mamilos/cirurgia , Valor Preditivo dos Testes , Cuidados Pré-OperatóriosRESUMO
Luminal breast cancer, as defined by oestrogen and/or progesterone expression by immunohistochemistry, accounts for up to 75% of all breast cancers. In this population, endocrine therapy is likely to account for most of the gains obtained with the administration of adjuvant systemic treatment. The role of adjuvant chemotherapy in these patients remains debatable since it is known that only a small fraction of patients will derive meaningful benefit from this treatment whilst the majority will be exposed to significant and unnecessary chemotherapy-related toxicities, in particular the elderly and frail. Therefore, neoadjuvant endocrine therapy (NET) becomes an attractive option for selected patients with hormonal-receptor positive locally advanced breast cancer. In this review, we discuss the current role of NET and future perspectives in the field.
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A angiogênese tem papel fundamental no crescimento tumoral. Células neoplásicas secretam fator de crescimento do endotélio vascular (vascular endothelial growthfactor - VEGF-A), estímulo para formação de nova vascularização, que promove suprimento sanguíneo às células tumorais e permite seu crescimento, invasão e metastatização. Os inibidores da angiogênese agem por meio da ligação inibitória ao VEGF (bevacizumabe) ou bloquando o receptor do VEGF-A (sunitinibe e sorafenibe). Seus efeitos antiangiogênicos incluem regressão e inibição da formação de neovasos. Essas medicações atualmente têm ampla utilização em terapias oncológicas. São agentes comercializados pela primeira vez em câncer colorretal metastático (becacizumabe) em 2004, mas que vêm desde então expandindo suas indicações: câncer de pulmão metastático (2006), carcinoma de células renais (2006), câncer de mama metastático (2008), glioblastoma multiforme recidivado (2008) e hepatocarcinoma avançado (2008). estudos atuais investigam o impacto da introdução desses agentes de maneira cada vez mais precoce na evolução da doença. Com isso, aumentam o tempo de exposição dos pacientes ao medicamento e o risco de seus efeitos colaterais. Viabiliza-se, portanto, o surgimento dos efeitos adversos tardios, até então pouco conhecidos, exigindo vigilância constante tanto clínica como epidemiológica. Os efeitos adversos...
Venous thromboembolism is a serious and potentially fatal disorder, which complicates the course of 20% of cancer patients, and has a significant impact on the quality of life and clinical outcomes of these patients. The pathophysiology of the association between thrombosis and cancer is complex. Malignancy is associated with a baseline hypercoagulable state secondary to the release of inflammatory cytokines, activation of the clotting system, expression of hemostatic proteins on tumor cells, inhibition of natural anticoagulants and impaired fibrinolysis. Several risk factors have been identified as contributing to venous thromboembolism and may be related to the patient characteristics, to the disease, and to the therapeutic interventions. The use of heparins and fondaparinux is indicated for selected cancer patients according to the types of malignancies and treatments. The treatment of venous thromboembolism in patients with cancer is challenging: the complications associated with the use of anticoagulants are significantly higher, may interfere with anticancer therapy and have a negative impact on quality of life.