The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients

BackgroundBreast 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.MethodsWe 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]).ResultsEvaluation 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.ConclusionWe 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

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Return to work after breast cancer diagnosis: experience of a cancer institute from the unified health system (SUS) in Brazil

Introdução: Câncer de mama é o mais comum em mulheres. Embora sua incidência ainda esteja em ascensão, as taxas de recorrência e mortalidade têm diminuído, em especial nos países desenvolvidos. Assim o câncer pode ser considerado um choque transitório que não impede que os sobreviventes retomem a normalidade em suas vidas, incluindo atividades laborais. Na América do Norte e Europa, as taxas de RT entre as pacientes com câncer de mama variam de 24-66% após 6 meses e 53-82% após 36 meses de diagnóstico. Os fatores mais associados ao RT são: idade, quimioterapia, sequelas da terapia do câncer e apoio do empregador e colegas de trabalho. Esses achados, no entanto, variam sugerindo que outros fatores e até aspectos de diferentes legislações podem interferir no RT. Na América Latina há escassez de dados sobre RT após o diagnóstico de câncer de mama. Objetivos: Avaliar as taxas de retorno ao trabalho nos meses 12 e 24 após o diagnóstico de câncer de mama e verificar a correlação de fatores à retomada ao trabalho aos 24 meses. Métodos: Estudo prospectivo observacional avaliando taxas de RT em mulheres com câncer de mama tratadas no Instituto do Câncer do estado de São Paulo, com idade > 18 e = 02 salários mínimos (OR 17,76, IC95% 3,33-94,75, p 0,001), cirurgia conservadora da mama (OR 9,77, IC 95% 2,03-47,05, p 0,004) e oferta de ajuste no trabalho pelo empregador (OR 37,62, IC95% 2,03-47,05, p 0,004). Fatores que se associaram de forma negativa ao RT foram: terapia endócrina (OR 0,11, IC95%0,02-0,74, p 0,023) e diagnóstico de depressão após o câncer (OR 0,07, IC95% 0,01-0,63, p 0,017). Conclusões: As taxas de RT aos 12 e 24 meses após diagnóstico de câncer de mama são inferiores a maioria dos estudos conduzidos na América do Norte e Europa. Oferta de ajuste no trabalho, maior renda familiar, cirurgia conservadora da mama, terapia endócrina adjuvante e diagnóstico de depressão após o câncer de mama desempenharam importante papel no RTBackground: Breast cancer is the most common cancer in women. While its incidence has been increasing, recurrence and mortality rates have been decreasing, mainly because of better treatment options. Because of that cancer can be regarded as a transient shock that does not prevent survivors resume normality in their lives including return to their workplace. In North America and Europe return to work (RTW) rates vary among breast cancer patients from 24- 66% after 06 months and 53-82% after 36 months of diagnosis. Factors most associated with the decision to return to work are: age, chemotherapy, sequelae related to cancer therapy and support from the employer and coworkers. However, these findings vary among the different populations evaluated, suggesting that other factors and even variations in countries laws may interfere with the decision to return to work. So far there is a lack of data on RTW after breast cancer diagnosis in Latin America. Endpoints: To evaluate return to work rates on months 12 and 24 after breast cancer diagnosis, and check the correlation of some factors with the decision to return to work at 24 months. Methods: A prospective, observational study evaluating RTW rates in patients with breast cancer diagnosis, > 18 and < 57 years old and a paid work for at least 03 months at the time of dianosis. Patients with inoperable or metastatic disease were excluded. On months 6, 12 and 24 they answered a telephone interview and the quality of life questionnaire (FACT-B). Results: Between july/2012 and september/2014, 125 patients were enrolled. Two of them died and two other could not be reached by telephone, and were excluded from the analysis. Mean age was 45,1 years (± 8,1). Most of them reported that they liked their job (94%) and received support from employer (73%), but only 29,1% reported having been offered work adjustment. Half of patients had stage II disease and 93% received chemotherapy as part of their treatment. Overall, 21,5%, 30,3% and 60,4% of patients returned to work 06, 12 and 24 months after breast cancer diagnosis, respectively. In the multivariate analysis, factors associated with positive RTW outcomes included higher income (OR: 17,76, CI95% 3,33-94,75; p = 0,001), breast conserving surgery (OR: 9,77, CI95% 2,03-47,05; p = 0,004) and work adjustment (OR: 37,62, CI95% 2,03-47,05; p= 0,004). Factors associated with negative RTW outcomes included adjuvant endocrine therapy (OR: 0,11, IC95% 0,02-0,74; p = 0,023) and depression diagnosis after breast cancer diagnosis (OR: 0,07, IC95% 0,01-0,63; p = 0,017). Conclusion: RTW rates after 12 and 24 months of breast cancer diagnosis are lower than reported in North America (with exception for low income americans) and Europe. Workplace adjustments, higher income, breast conserving surgery, endocrine therapy and depression after breast cancer played an important role in the RTW decisio

Non-alcoholic fatty liver disease and insulin resistance: importance of risk factors and histological spectrum.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-07-08T14:23:37Z No. of bitstreams: 1 Siqueira ACG Non-alcogolic....pdf: 83109 bytes, checksum: 5b111d26fb2bf982f064436a2567a53b (MD5)Made available in DSpace on 2014-07-08T14:23:37Z (GMT). No. of bitstreams: 1 Siqueira ACG Non-alcogolic....pdf: 83109 bytes, checksum: 5b111d26fb2bf982f064436a2567a53b (MD5) Previous issue date: 2005Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been associated with several metabolic conditions (MC) and secondary causes, but the relationship between insulin resistance (IR) and the underlying aetiology of NAFLD has not been extensively explored. OBJECTIVE: To determine the frequency of IR among NAFLD patients and to describe IR according to risk factors and histological findings of the disease. METHODOLOGY: A case-series study of 64 patients with clinical and histological diagnosis of NAFLD. IR was calculated by homeostasis model assessment (HOMA) and IR was considered when HOMA > or = 3. Histological grades of NAFLD were: stage 1, steatosis isolated; stage 2, steatosis and inflammation; stage 3, steatosis and ballooning degeneration; stage 4, steatosis and fibrosis and/or Mallory bodies. Fibrosis was graded 0-4 (cirrhosis). RESULTS: IR was found in 21 (33%) patients. Among those with IR, 16 patients (76%) had associated MC and five patients (24%) had exposure to petrochemicals. The mean value of HOMA varied from 3.5 in NAFLD associated with MC to 1.6 in patients with exposure to petrochemicals (P < 0.03). Waist circumference was the metabolic factor most strongly associated with IR (P < 0.005). Steatohepatitis (NASH) was observed in 54 (84.3%) cases. The HOMA mean value was significantly higher in patients with advanced fibrosis. CONCLUSIONS: IR occurred in 33% of the NAFLD patients, being more frequent among those with MC than among those with exposure to petrochemicals. The presence of IR in cases with advanced fibrosis suggests that it may influence the prognosis of NAFLD

Depleção de célula B no tratamento de citopenias auto-imunes B-Cell depletion in the treatment of autoimmune cytopenias

A morbidade associada ao tratamento de citopenias auto-imunes tornou necessária a busca por novas terapêuticas. Baseado no fato de que o rituximab reage especificamente contra o antígeno CD 20, induzindo depleção de células B e conseqüentemente levando à diminuição na produção de auto-anticorpos, cinco pacientes com citopenias auto-imunes foram tratados com esta droga. Os pacientes eram refratários à terapia convencional e receberam 375 mg/m² de rituximab semanalmente, por um período de quatro semanas. Todos os pacientes apresentaram melhora, seja pelo aumento do número de células (níveis de hemoglobina ou contagem de plaquetas), seja pela suspensão do uso de corticoesteróides. Não foram observadas reações importantes durante infusão do medicamento, ou mesmo episódios de infecção durante acompanhamento subseqüente. Desta forma, o rituximab se mostrou eficaz e seguro para pacientes portadores de anemia hemolítica e púrpura trombocitopênica de etiologia imunológica, sugerindo que esta droga deva fazer parte do arsenal terapêutico utilizado nestas doenças auto-imunes.The morbidity associated with the treatment of autoimmune cytopenias has created a need for new approaches. Based on the fact that rituximab reacts specifically against the CD 20 antigen and induces B-cell depletion interfering with the production of auto-antibodies, five patients with autoimmune cytopenias were treated. All patients were previously refractory to conventional therapy and received 375 mg/m² of rituximab infusion weekly, for four weeks. All patients improved either by increasing the number of cells or by being able to reach steroid suspension. No major reactions occurred during infusion, and no major infections occurred during the follow up. Rituximab appears to be active and safe for patients with autoimmune hemolytic anemia and thrombocytopenia, suggesting that this agent can play an important part in the therapeutic arsenal for autoimmune diseases