The journey of stage III and IV non-small cell lung cancer patients in the Brazilian private healthcare system: a retrospective study.

Non-small cell lung cancer (NSCLC) is still diagnosed at late stages in Brazil. The availability of newer treatment options has changed patient management, however, few real-world data have been published since then. This is a population-based retrospective cohort study that aims to evaluate the characteristics of stage III/IV NSCLC patients and their journey in the Brazilian private healthcare system. Patients aged ≥18 years, residing in Brazil who had their first medical appointment between 2016 and 2018 were included in the study. The sociodemographic and clinical characteristics of the patients and time intervals of interest were described. A total of 10,394 patients were analyzed. The majority of the patients were male (58.5%) with a median age of 64.0 (IQR = 58.0 - 71.0) years. In relation to characteristics of the disease, most of the tumors were characterized as adenocarcinomas (52.3%) and diagnosed at stage IV (72.2%). Most patients arrived at the hospital with an established NSCLC diagnosis, while 45.7% were diagnosed at the first medical appointment in the hospital or later. For patients who were diagnosed at the first medical appointment or later, a median interval of 15.0 (IQR = 6.0 - 33.0) days was observed between the first medical appointment and the diagnosis. The first treatment was given after a median of 25.0 (IQR = 6.0 - 49.0) days after diagnosis for patients without a prior diagnosis, and 57.0 (IQR: 33.0 - 98.0) days for patients with a prior diagnosis. The most common treatments were chemotherapy alone (33.8%), chemotherapy combined with radiotherapy (21.5%), radiotherapy alone (13.1%), adjuvant or neoadjuvant treatment (9.3%), surgery (3.3%), and immunotherapy (0.7%; alone or combined). At the end of follow-up (September, 2020), 52.3% of the patients had died. Despite having more treatment options in the private sector, data show that there is a need to improve access to technologies.

EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing.

PURPOSE: There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. RESULTS: A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%-18.7% depending on the sequencing method). CONCLUSION: This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.

Real-World Molecular Testing and Treatment Patterns in Brazilian Patients with Newly Diagnosed Locally Advanced or Metastatic NSCLC.

OBJECTIVES: To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naïve patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naïve patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. RESULTS: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a 'former' or 'current smoker'. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1%), while non-platinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). CONCLUSION: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.

Oncology practice during COVID-19 pandemic: a fast response is the best response.

The first confirmed case of coronavirus disease 2019 (COVID-19) in Brasil was reported on February 25th, 2020, and by April 3rd, 8076 were confirmed in the country. As COVID-19 disease incidence escalates in Brasil, management of cancer patients requires immediate action and oncology clinics are urged to establish a contingency plan. We have installed a COVID-19 Management Committee to elaborate and implement best practices to assist cancer outpatients as well as to provide a safe environment for clinical staff and other employees at the outpatient clinics. The challenges of cancer treatment in the midst of COVID-19 global pandemic highlight the importance of a rapid response by institutions, where organizational structure, strategic planning, agility in guidelines implementation and alternative ways to protect and support clinical staff, employees and patients may be the key to mitigate pandemic effects.

Oncology practice during COVID-19 pandemic: a fast response is the best response

SUMMARY The first confirmed case of coronavirus disease 2019 (COVID-19) in Brasil was reported on February 25th, 2020, and by April 3rd, 8076 were confirmed in the country. As COVID-19 disease incidence escalates in Brasil, management of cancer patients requires immediate action and oncology clinics are urged to establish a contingency plan. We have installed a COVID-19 Management Committee to elaborate and implement best practices to assist cancer outpatients as well as to provide a safe environment for clinical staff and other employees at the outpatient clinics. The challenges of cancer treatment in the midst of COVID-19 global pandemic highlight the importance of a rapid response by institutions, where organizational structure, strategic planning, agility in guidelines implementation and alternative ways to protect and support clinical staff, employees and patients may be the key to mitigate pandemic effects.

RESUMO O primeiro caso confirmado de Doença Associada ao Coronavírus 2019 (COVID-19) no Brasil foi confirmado em 25 de fevereiro de 2020 e em 3 de abril já haviam 8076 casos confirmados no país. A medida que a incidência de COVID-19 aumenta no Brasil, o tratamento de pacientes com câncer exige ação imediata e as clínicas oncológicas são instadas a estabelecer um plano de contingência. Instalamos um Comitê de Manejo de COVID-19 para elaborar e implementar as melhores práticas para ajudar pacientes ambulatoriais com câncer, bem como proporcionar um ambiente seguro para a equipe clínica e outros funcionários das clínicas ambulatoriais. Os desafios do tratamento do câncer em meio à pandemia global do COVID-19 destacam a importância de uma resposta rápida das instituições, onde a estrutura organizacional, o planejamento estratégico, a agilidade na implementação de diretrizes e formas alternativas de proteger e apoiar a equipe clínica, funcionários e pacientes podem ser a chave para mitigar os efeitos da pandemia.

Real-world molecular testing and treatment patterns in brazilian patients with newly diagnosed locally advanced or metastatic NSCLC

OBJECTIVES: To evaluate the molecular testing and treatment patterns in a retrospective cohort of newly diagnosed treatment-naïve patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHODS: This is an observational retrospective cohort study conducted across 10 cancer centers in Brazil. Treatment-naïve patients with locally advanced or metastatic NSCLC were enrolled from January to December 2014. The following data were collected from the medical records of patients from diagnosis until the last record (death, loss to follow-up, or the end of the maximum follow-up period): demographics; medical history; smoking status; disease characteristics; previous treatments; and molecular testing patterns and results. The overall survival (OS) was also estimated. Results: A total of 391 patients from 8 different Brazilian states were included, with a median age of 64.1 years (23.7-98.7), with most patients being males (60.1%). The smoking status of 74.2% of patients was a 'former' or 'current smoker'. Stage IV NSCLC at diagnosis was observed in 82.4% of patients, with 269 of them (68.8%) presenting adenocarcinoma (ADC). Among the stage IV ADC patients, 54.0% were referred for molecular testing. Among the patients with an available epidermal growth factor receptor (EGFR) mutation status, 31 (24.0%) were EGFR-positive. The first-line treatment was a platinum-based chemotherapy for 98 patients (25.1%), while non-platinum-based regimens were used in 54 patients (13.8%). OS data were available for 370 patients, with a median OS of 10.8 months. Never smokers had a significantly higher median OS versus current or former smokers (14.6 versus 9.1 months; log-rank p=0.003). Among the patients for whom molecular testing data were available, those with EGFR-positive results had a longer median OS (34.6 versus 12.8 months; log-rank p=0.003). Conclusion: Our findings provide relevant information for prescribers and policy decision-makers by highlighting the unmet needs of patients and the importance of molecular testing in newly diagnosed locally advanced or metastatic lung adenocarcinoma. We also highlight the respective EGFR-tyrosine kinase inhibitor treatment when the result is positive and the areas in which further efforts are required to grant access to effective treatment.

Cervical cancer control in Latin America: A call to action.

Cervical cancer (CC) is second most common cause of cancer in Latin America and is a leading cause of cancer mortality among women. In 2015, an estimated 74,488 women will be diagnosed with CC in Latin America and 31,303 will die of the disease. CC mortality is projected to increase by 45% by 2030 despite human papillomavirus (HPV) vaccination and screening efforts. In this setting, the goal was of the current study was to examine CC control efforts in Latin America and identify deficiencies in these efforts that could be addressed to reduce CC incidence and mortality. The authors found that HPV vaccination has been introduced in the majority of Latin American countries, and there is now a need to monitor the success (or shortcomings) of these programs and to ensure that these programs are sustainable. This topic was also reviewed in light of emerging data demonstrating that visual inspection with acetic acid and HPV DNA testing without Papanicolaou tests have efficacy from a screening perspective and are good alternatives to cytology-based screening programs. Overall, there is a need to build capacity for CC control in Latin America and the best strategy will depend on the country/region and must be tailored to meet the needs of the population as well as available resources.

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.

Caracterização físico-química da acidose metabólica induzida pela expansão volêmica inicial com solução salina a 0,9 por cento em pacientes com sepse grave e choque séptico / Physicochemical characterization of metabolic acidosis induced by normal saline resuscitation of patients with severe sepsis and septic shock

OBJETIVO: O objetivo deste estudo foi caracterizar e quantificar a acidose metabólica causada pela expansão volêmica inicial na reanimação de pacientes com sepse grave e choque séptico. MÉTODOS: Uma coleta de sangue para caracterização físico-química do equilíbrio ácido-básico antes e após a expansão volêmica com 30 mL/kg de solução salina a 0,9 por cento. O diagnóstico e a quantificação da acidose metabólica foram feitas com o uso do "standard base excess" (SBE). RESULTADOS: Oito pacientes com 58 ± 13 anos e APACHE II de 20 ± 4 foram expandidos com 2000 ± 370 mL de solução salina a 0,9 por cento. Houve queda do pH de 7,404 ± 0,080 para 7,367 ± 0,086 (P=0,018) associada a elevação da PCO2 de 30 ± 5 mmHg para 32 ± 2 mmHg (P=0,215) e queda do SBE de -4,4 ± 5,6 para -6,0 ± 5,7 mEq/L (P=0,039). Esta queda do SBE foi associada ao poder acidificante de dois fatores: elevação não significativa do "strong ion gap" (SIG) de 6,1 ± 3,4 para 7,7 ± 4,0 mEq/L (P=0,134) e queda não significativa do "strong ion diference" aparente inorgânico (SIDai) de 40 ± 5 para 38 ± 4 mEq/L (P=0,318). Em contraposição, houve queda da albumina sérica de 3,1 ± 1,0 para 2,6 ± 0,8 mEq/L (P=0,003), que teve um poder alcalinizante sobre o SBE. A elevação do cloro sérico de 103 ± 10 para 106 ± 7 mEq/L (P<0,001) gerou a queda do SIDai. CONCLUSÃO: A reanimação inicial de pacientes com sepse grave e choque séptico com 30 mL/Kg de solução salina a 0,9 por cento é associada a piora da acidose metabólica aferida pelo SBE. Esta piora do SBE pode ser atribuída a uma elevação dos ânions não mensuráveis e do cloro sérico.

OBJECTIVE: The aim of this study was to characterize and quantify metabolic acidosis that was caused by initial volume expansion during the reanimation of patients with severe sepsis and septic shock. METHODS: A blood sample was drawn for physicochemical characterization of the patient's acid-base equilibrium both before and after volume expansion using 30 mL/kg 0.9 percent saline solution. The diagnosis and quantification of metabolic acidosis were based on the standard base excess (SBE). RESULTS: Eight patients with a mean age of 58 ± 13 years and mean APACHE II scores of 20 ± 4 were expanded using 2,000 ± 370 mL of 0.9 percent saline solution. Blood pH dropped from 7.404 ± 0.080 to 7.367 ± 0.086 (p=0.018), and PC O2 increased from 30 ± 5 to 32 ± 2 mmHg (p=0.215); SBE dropped from -4.4 ± 5.6 to -6.0 ± 5.7 mEq/L (p=0.039). The drop in SBE was associated with the acidifying power of two factors, namely, a significant increase in the strong ion gap (SIG) from 6.1 ± 3.4 to 7.7 ± 4.0 mEq/L (p = 0.134) and a non-significant drop in the apparent inorganic strong ion differences (SIDai) from 40 ± 5 to 38 ± 4 mEq/L (p = 0.318). Conversely, the serum albumin levels decreased from 3.1 ± 1.0 to 2.6 ± 0.8 mEq/L (p = 0.003) with an alkalinizing effect on SBE. Increased serum chloride levels from 103 ± 10 to 106 ± 7 mEq/L (p < 0.001) led to a drop in SIDai. CONCLUSION: Initial resuscitation using 30 mL/kg of 0.9 percent saline solution for patients with severe sepsis and septic shock is associated with worsened metabolic acidosis, as measured by SBE. This worsened SBE can be ascribed to a serum increase in the levels of unmeasurable anions and chloride.

Management of anemia in cancer patients.

Cancer-related anemia adversely affects quality of life and is associated with reduced overall survival. The correction of anemia in cancer patients has the potential to improve treatment efficacy and increase survival. A large number of studies demonstrate that treatment of anemia in cancer patients using erythropoiesis-stimulating agents (ESAs) significantly increases hemoglobin levels, decreases transfusion requirements and improves quality of life, predominantly by reducing fatigue. Some data on the use of ESAs in cancer patients indicate an increased risk of thromboembolic events and a possibly increased risk of mortality. However, there is ample evidence that when ESAs are used within current guidelines, they are valuable and safe drugs for the treatment of anemia in patients receiving radiotherapy and/or chemotherapy. There are increasing data from prospective, randomized trials demonstrating better responses to ESAs with the concurrent use of iron. Blood transfusions are also helpful in the management of anemia in cancer patients, especially when there is a need for immediate increases in hemoglobin levels. In this article, we discuss recent aspects relating to treatment modalities for anemia in cancer patients.

Physicochemical characterization of metabolic acidosis induced by normal saline resuscitation of patients with severe sepsis and septic shock. / Caracterização físico-química da acidose metabólica induzida pela expansão volêmica inicial com solução salina a 0,9% em pacientes com sepse grave e choque séptico.

OBJECTIVE: The aim of this study was to characterize and quantify metabolic acidosis that was caused by initial volume expansion during the reanimation of patients with severe sepsis and septic shock. METHODS: A blood sample was drawn for physicochemical characterization of the patient's acid-base equilibrium both before and after volume expansion using 30 mL/kg 0.9% saline solution. The diagnosis and quantification of metabolic acidosis were based on the standard base excess (SBE). RESULTS: Eight patients with a mean age of 58 ± 13 years and mean APACHE II scores of 20 ± 4 were expanded using 2,000 ± 370 mL of 0.9% saline solution. Blood pH dropped from 7.404 ± 0.080 to 7.367 ± 0.086 (p=0.018), and PC O2 increased from 30 ± 5 to 32 ± 2 mmHg (p=0.215); SBE dropped from -4.4 ± 5.6 to -6.0 ± 5.7 mEq/L (p=0.039). The drop in SBE was associated with the acidifying power of two factors, namely, a significant increase in the strong ion gap (SIG) from 6.1 ± 3.4 to 7.7 ± 4.0 mEq/L (p = 0.134) and a non-significant drop in the apparent inorganic strong ion differences (SIDai) from 40 ± 5 to 38 ± 4 mEq/L (p = 0.318). Conversely, the serum albumin levels decreased from 3.1 ± 1.0 to 2.6 ± 0.8 mEq/L (p = 0.003) with an alkalinizing effect on SBE. Increased serum chloride levels from 103 ± 10 to 106 ± 7 mEq/L (p < 0.001) led to a drop in SIDai. CONCLUSION: Initial resuscitation using 30 mL/kg of 0.9% saline solution for patients with severe sepsis and septic shock is associated with worsened metabolic acidosis, as measured by SBE. This worsened SBE can be ascribed to a serum increase in the levels of unmeasurable anions and chloride.

Deficiencia de ferro no paciente com câncer: [revisão] / Iron deficiency in cancer patients: [review]

Anemia é uma complicação quase universal nos pacientes em estágios avançados de doença renal crônica (DRC). Ela está associada com maior número de internações hospitalares, maior mortalidade e pior qualidade de vida dos pacientes. Ela tem várias causas, sendo deficiência de eritropoetina e ferro as duas principais causas. A condição inflamatória presente na DRC interfere com a ação da eritropoetina e com a absorção intestinal de ferro e mobilização de ferro dos estoques, devido ao aumento de hepcidina. A correção parcial (não completa) da anemia promove melhores resultados nos pacientes com DRC.

Anemia is an almost universal complication of patients in advanced stages of chronic kidney disease (CKD). It is associated with more hospitalizations, increased mortality and worse quality of life. Although there are several causes, erythropoietin and iron deficiency are the most common. The inflammatory condition present in CKD interferes with the action of erythropoietin, intestinal iron absorption and iron mobilization from deposits, due to increased hepcidin concentrations. Partial but incomplete correction of anemia promotes better outcomes in patients with CKD.

Determinação da frequência de polimorfismos de cyp2d6 em mulheres brasileiras e revisão de literatura / Determination of the frequency of CYP2D6 polymorphisms in Brazilian women and literature review

O tamoxifeno (TMX),consagrado como terapia padrão no tratamento de pacientes portadoras de câncer de mama com receptores hormonais positivos, é convertido por metabolização primária e secundária no metabólito endoxifeno, que apresenta afinidade muito maior pelos receptores hormonais e é o maior responsável pelos efeitos antitumorais desta droga. A biotransformação do TMX em endoxifeno é dependente da subunidade 2D6 do citocromo P-450 (CYP2D6), cujo gene apresenta inúmeros polimorfismos que reduzem a atividade metabólica dessa via biológica, resultando em menores níveis de seu produto ativo e, possivelmente, da resposta terapêutica ao uso do TMX. Objetivo: O objetivo deste estudo foi determinar a frequência dos polimorfismos CYP2D6*3, *4, *5, *6 e *10 e dos fenótipos de metabolização da droga TMX em pacientes portadoras de câncer de mama atendidas pelos autores no Centro de Oncologia do Hospital Sírio Libanês (HSL), além de revisar os dados sobre este tema disponíveis na literatura. Métodos: Amostras de sangue periférico de 30 pacientes foram enviadas a laboratório de referência para pesquisa dos polimorfismos descritos de CYP2D6 pela técnica de reação em cadeia da polimerase e digestão por enzimas de restrição (PCR-RFLP). Resultados: Os resultados mostraram heterozigose para polimorfismo CYP2D6*4 e *10 em 33 e 38% das mulheres, respectivamente. Utilizando a classificação de fenótipos de metabolização de TMX previamente descrita determinamos que 27% das mulheres avaliadas foram categorizadas com perfil de metabolização intermediária da droga, e 3% como metabolizadoras pobres, as quais, segundo dados atuais, parecem estar duas vezes mais sujeitas a desenvolverem recorrência de câncer de mama durante tratamento com TMX. Foi documentada uma elevada e inesperada prevalência de heterozigose do polimorfismo *10 na população estudada. Conclusões: Estudos prospectivos estão em andamento, visando definir o papel do perfil dos polimorfismos de CYP2D6 na escolha...

Tamoxifen (TMX), established as standard therapy in treating patients with breast cancer with hormone receptor positive, is converted by metabolism in primary and secondary metabolite endoxifeno, which has much higher affinity for hormone receptors and is most responsible the antitumor effects of this drug. Biotransformation of TMX in endoxifeno 2D6 is dependent on the subunit of cytochrome P-450 (CYP2D6), whose gene has many polymorphisms that reduce the metabolic activity of this biological pathway, resulting in lower levels of its active product, and possibly therapeutic response to use of TMX. Objective: The objective of this study was to determine the frequency of CYP2D6 polymorphisms * 3, * 4, * 5, * 6 and * 10 and phenotypes of drug metabolizing TMX in patients with breast cancer treated by the authors at the Centre for Oncology Syrian Lebanese Hospital (HSL), and review the data on this subject available in the literature. Methods: Blood samples from 30 patients were sent to reference laboratory for research of CYP2D6 polymorphisms described the technique of polymerase chain reaction and restriction enzyme digestion (PCR-RFLP). Results: Results showed heterozygosity for polymorphic CYP2D6 * 4 and * 10 in 33 women and 38% respectively. Using the classification of phenotypes of metabolism of TMX described previously determined that 27% of the women studied were categorized with a profile of intermediate metabolites of the drug, and 3% as poor metabolizers, which, according to current data seem to be two times more likely to develop recurrence of breast cancer during treatment with TMX. It was documented and an unexpected high prevalence of heterozygous * 10 polymorphism in the population. Conclusions: Prospective studies are underway, aimed at defining the role of the profile of CYP2D6 polymorphisms on the choice of strategy hormonal therapy in women with breast cancer.

Insuficiência cardíaca induzida pela quimioterapia: mecanismos e tratamentos / Chemotherapy-induced heart failure: mechanisms and treatments

Nas últimas décadas, o advento de estratégias de tratamento para diversos tipos de tumores permitiu aos pacientes oncológicos longa sobrevida, possibilitando o desenvolvimento de complicações cardiovasculares em grande número de pacientes. A incidência e a gravidade das lesões dependem do quimioterápico administrado, da dose cumulativa empregada, da presença prévia ou não de cardiomiopatias, da existência de comorbidades e da utilização de outros tratamentos utilizados, tais como a radioterapia. A quimioterapia pode levar a toxicidade cardiovascular, manisfestada pela ocorrência de miocardiopatia com ou sem insuficiência cardíaca, disfunção endotelial e arritmias. Apesar de os efeitos dos quimioterápicos e de a incidência de cardiomiopatia estarem bem documentados, ainda não existem estudos específicos direcionados para o tratamento dessa população de pacientes. A base do tratamento proposto tem sido a mesma utilizada para outras formas de agressões miocárdicas, ou seja, fundamentada no uso de inibidor da enzima de conversão. betabloqueador e diuréticos.

Over the last decades, the advent of new and effective treatments for different tumor types has enabled oncologic patients to live longer, however, a large number of these patients develop cardiovascular complications. The incidence and severity of the lesions depend on the type of chemotherapy drug used, cumulative dose, presence of coexisting cardiac disease, others co- morbidities and the association with other treatments such as radiotherapy. Chemotherapy may lead to cardiovascular toxicity, which is manifested by cardiomyopathy with or without heart failure, endothelial lesion and arrhythmias. Although the potential cardiac effects of chemotherapy and cardiomyopathy have been well documented, there is a lack of specific studies focusing on the treatment of this population of patients. The proposed therapy has been the same as that used in other types of myocardial lesions, i.e., the use of angiotensin converting enzyme, betablockers and diuretics.

Câncer de mama triplo-negativo: aspectos clínicos, laboratoriais e terapêuticos: [revisão] / Triple negative breast cancer: clinical, loboratorial and therapeutic aspects: [review]

O câncer de mama é a neoplasia maligna mais comum entre as mulheres, e sua incidência vem aumentando de maneira consistente nas últimas décadas. A melhor compreensão anatomopatológica e molecular do câncer de mama vem permitindo observar que os diferentes subtipos desta doença apresentam características clínicas e prognósticas diferentes, além de perfil de resposta aos tratamentos diferenciados para cada subtipo. Neste artigo, serão revistos os principais aspectos clínicos, laboratoriais e terapêuticos do subgrupo de câncer de mama triplo-negativo; subgrupo de doença definido, do ponto de vista imunoistoquímico, pela ausência de receptores hormonais ou de HER-2. Esse tipo de câncer de mama representa novo desafio para os profissionais envolvidos no tratamento multidisciplinar dessa neoplasia, e vem tornando-se foco de inúmeros estudos destinados a permitir sua melhor compreensão e ao desenho de estratégias terapêuticas mais eficientes.

Breast cancer is the most common cancer among women; the incidence of such disease is increasing through the last decades. Recently, several advances regarding the understanding of the pathology and molecular biology of breast cancer directed us to a new understanding of the disease pathologic mechanisms, leading to a molecular classification and, consequently, a novel way to treat the patients. In this review we will focus on the main clinical, laboratorial and therapeutical aspects of the triple negative breast cancer, as well as on the differences and similarities among triple negative, basal-like and BRCA1 linked breast cancers.