RESUMO
BACKGROUND: Poly(ADP-ribose)polymerase-1 (PARP-1) is a highly promising novel target in breast cancer. However, the expression of PARP-1 protein in breast cancer and its associations with outcome are yet poorly characterized. PATIENTS AND METHODS: Quantitative expression of PARP-1 protein was assayed by a specific immunohistochemical signal intensity scanning assay in a range of normal to malignant breast lesions, including a series of patients (N = 330) with operable breast cancer to correlate with clinicopathological factors and long-term outcome. RESULTS: PARP-1 was overexpressed in about a third of ductal carcinoma in situ and infiltrating breast carcinomas. PARP-1 protein overexpression was associated to higher tumor grade (P = 0.01), estrogen-negative tumors (P < 0.001) and triple-negative phenotype (P < 0.001). The hazard ratio (HR) for death in patients with PARP-1 overexpressing tumors was 7.24 (95% CI; 3.56-14.75). In a multivariate analysis, PARP-1 overexpression was an independent prognostic factor for both disease-free (HR 10.05; 95% CI 5.42-10.66) and overall survival (HR 1.82; 95% CI 1.32-2.52). CONCLUSIONS: Nuclear PARP-1 is overexpressed during the malignant transformation of the breast, particularly in triple-negative tumors, and independently predicts poor prognosis in operable invasive breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Núcleo Celular/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patologia , Núcleo Celular/patologia , Células Cultivadas , Progressão da Doença , Embrião de Mamíferos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases , Poli(ADP-Ribose) Polimerases/genética , Prognóstico , RNA Interferente Pequeno/farmacologia , Análise de Sobrevida , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
BACKGROUND: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer. PATIENTS AND METHODS: We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab. RESULTS: Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia. CONCLUSIONS: Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade ≥ 3 arterial or venous thromboembolic events, GI perforation, or fatal events.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Algoritmos , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Neoplasias da Mama/epidemiologia , Carcinoma/epidemiologia , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Fatores de RiscoRESUMO
PURPOSE: We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain. METHODS: This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM. RESULTS: We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department. CONCLUSION: Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes. CLINICAL TRIAL REGISTRATION: Not applicable.
Assuntos
Registros Eletrônicos de Saúde/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Atitude do Pessoal de Saúde , Estudos Transversais , Prescrição Eletrônica/estatística & dados numéricos , Humanos , Relações Médico-Paciente , Qualidade da Assistência à Saúde , Espanha , Inquéritos e Questionários/estatística & dados numéricos , Carga de TrabalhoRESUMO
Cancer is one of the major public health problems in our society. It is estimated that more than 18 million new cases are diagnosed worldwide every year; 280,000 in Spain. Incidence in following a growing trend. This epidemic could be controlled with research into new treatments and, above all, with adequate prevention. Primary prevention could prevent avoid up to half of all cases. For many others, secondary prevention is essential, as it make diagnosis possible in the stages of the disease when it is easily curable. These guidelines present the scientific evidence regarding secondary prevention in tumors in which its use is well-accepted: breast, cervical, colorectal, prostate, lung, ovarian, melanoma, and gastric cancer.