PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

<p>Abstract</p> <p>Background</p> <p>The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality.</p> <p>Methods</p> <p>In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor.</p> <p>Results</p> <p>Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009).</p> <p>Conclusion</p> <p>Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients.</p

Metástases Endobrônquicas â Experiência em dois hospitais terciários

RESUMO: Os autores decidiram determinar a frequência de metástases endobrônquicas (M.ED) em doentes com história clínica de doença maligna extratorácica.Realizaram um estudo retrospectivo de 2836 broncofibroscopias (BFB) realizadas nos serviços de pneumologia e cirurgia cardio-torácica de dois hospitais terciários da Cidade do México.Só foram incluídos no estudo os doentes que revelaram lesões tumorais endobrônquicas com história prévia de doença maligna extratorácica. Todos os doentes tinham sintomas respiratórios e alterações na radiografia do tórax.De 911 doentes que mostraram alterações endoscópicas de neoplasia só 58 doentes tinham metástases endobrônquicas.Estes doentes foram todos submetidos a biópsias, lavados e escovados. O tempo de evolução, o tratamento e a sobrevivência foram registados.As M.ED foram mais frequentes nas mulheres (36 mulheres para 28 homens). A média de idades foi 52,8 anos. 51% das M.ED estavam localizadas na arvore brônquica direita. A traqueia estava envolvida em 20% dos casos. As M.ED mais frequentes eram do útero, mama e rim. A biópsia brônquica teve 84,9% de sensibilidade.A metástase endobrônquica isolada foi rara sendo geralmente acompanhada de outas metástases intratorácicas. A metástase endobrônquica do carcinoma do colo do útero é a mais frequente nesta série.A BFB foi o método de grande utilidade no diagnóstico das metástases endobrônquicas neste estudo.O tratamento das M.ED foi paliativo sendo a cirurgia apenas num caso. COMENTÃRIO: Os tumores malignos extratorácicos podem metastizar para o pulmão, para os gânglios hilares e mediastínicos e para a pleura.As metástases endobrônquicas macroscópicas são raras e estão presentes em apenas 5% dos doentes com tumores malignos extratorácicos.A origem mais frequente é dos tumores do rim, mama e cólon. Em mais de 30% dos casos coincidem com outras metástases intratorácicas.A importância do diagnóstico endobrônquico e anátomo-patológico está relacionado com a importância de saber se é um tumor primitivo do pulmão, um tumor benigno ou de facto uma metástase endobrônquica.A BFB continua a ser o método de eleição e obrigatório sempre que há sintomas respiratórios e/ou alterações na radiografia do tórax.Pensamos que este trabalho tem interesse parti-cularmente pelo número elevado de broncofibroscopias avaliadas e também por constatar que a origem mais frequente das metástases endobrônquicas está relacionada com o carcinoma do colo do útero, o que contraria as séries publicadas.Outro aspecto importante é o realce dado ao tratamento paliativo com o objectivo principal de melhorar a obstrução brônquica e, subsequente- mente, a qualidade de vida.Por fim, gostava de fazer uma referência à eventualidade do tratamento cirúrgico em casos pontuais e particulares da M.ED do carcinoma colorectal que atingiu o 'follow up' dos 32 meses sem qualquer sintoma ou sinal de recidiva. Palavras-chave: Broncofibroscopia, Metástase endobrônquica, Tumor maligno extratorácic

Medical care costs incurred by patients with smoking-related non-small cell lung cancer treated at the National Cancer Institute of Mexico

Background Smoking is a public health problem in Mexico and worldwide; its economic impact on developing countries has not been well documented. The aim of this study was to assess the direct medical costs attributable to smoking incurred by lung cancer patients treated at the National Cancer Institute of Mexico (INCan). Methods The study was conducted at INCan in 2009. We carried out a cost of illness (COI) methodology, using data derived from an expert panel consensus and from medical chart review. A panel of experts developed a diagnostic-therapeutic guide that combined the hospital patient pathways and the infrastructure, human resources, technology, and services provided by the medical units at INCan. Cost estimates in Mexican pesos were adjusted by inflation and converted into US Dollars using the 2013 FIX exchange rate for foreign transactions (1 USD = 13.06 Mexican pesos). Results A 297 incident cases diagnosed with any type of lung cancer were analyzed. According to clinical stage, the costs per patient were 13,456; 35,648; 106,186; and 144,555 USD, for lung cancer stages I, II, III, and IV respectively. The weighted average annual cost/patient was and 139,801 USD and the average annual cost/patient that was attributable to smoking was 92,269 USD. This cost was independent of the clinical stage, with stage IV representing 96% of the annual cost. The total annual cost of smoking-related lung cancer at INCan was 19,969,781 USD. Conclusions The medical care costs of lung cancer attributable to smoking represent a high cost both for INCan and the Mexican health sector. These costs could be reduced if all provisions established in the Framework Convention of Tobacco Control of the World Health Organization were implemented in Mexico