Characteristics and prognosis of stage I-III breast cancer subtypes in Brazil: The AMAZONA retrospective cohort study.

OBJECTIVE: To describe stage I-III breast cancer (BC) molecular subtypes and outcomes among a cohort of patients from Brazil. METHODS: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer, diagnosed in 2001 (n = 2198) and 2006 (n = 2714). In this analysis, we included patients who underwent surgery, had stage I-III disease and available pathological information (n = 2296). We estimated molecular subtypes by local immunohistochemical stains. Data was obtained from medical charts and public databases. RESULTS: Mean age at diagnosis was 54 years and 41.1% were younger than 50 years. 23.3% were diagnosed in stage I, 53.5% in stage II and 23.2% in stage III. 80.8% were treated in the public health system. 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. 55.6% were treated with mastectomy and 96.2% received adjuvant treatment (82.2% chemotherapy). 13.4% of HER-2 positive patients received adjuvant trastuzumab. Overall survival rate at 5 years was 96.84% for stage I, 94.16% for stage II and 70.48% for stage III. Molecular subtypes were independent prognostic factor in stages II and III patients. CONCLUSIONS: Brazilian women have a higher risk of being diagnosed with late stage breast cancer and younger age than in high-income countries. Luminal-like disease is the most common molecular subtype in the country. Triple negative and HER-2 positive had the worst prognosis.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up.

OBJECTIVE:: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS:: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS:: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS:: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients-Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group.

PURPOSE: The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. METHODS AND MATERIALS: A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. RESULTS: A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade ≥3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. CONCLUSIONS: The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study.

Translation and cross-cultural adaptation into Brazilian Portuguese of the Vanderbilt Head and Neck Symptom Survey version 2.0 (VHNSS 2.0) for the assessment of oral symptoms in head and neck cancer patients submitted to radiotherapy / Tradução e adaptação cultural para o português (Brasil) do instrumento Vanderbilt Head and Neck Symptom Survey version 2.0 (VHNSS 2.0) para avaliação de sintomas orais em pacientes com câncer de cabeça e pescoço submetidos à radioterapia

ABSTRACT INTRODUCTION: Patients submitted to radiotherapy for the treatment of head and neck cancer have several symptoms, predominantly oral. The Vanderbilt Head and Neck Symptom Survey version 2.0 is an American tool developed to evaluate oral symptoms in head and neck cancer patients submitted to radiotherapy. OBJECTIVE: The aim of the present study was to translate the Vanderbilt Head and Neck Symptom Survey version 2.0 into Brazilian Portuguese and cross-culturally adapt this tool for subsequent validation and application in Brazil. METHODS: A method used for the translation and cultural adaptation of tools, which included independent translations, synthesis of the translations, back-translations, expert committee, and pre-test, was used. The pre-test was performed with 37 head and neck cancer patients, who were divided into four groups, to assess the relevance and understanding of the assessed items. Data were submitted to descriptive statistical analysis. RESULTS: The overall mean of the content validity index was 0.79 for semantic and idiomatic equivalence, and it was higher than 0.8 for cultural and conceptual equivalence. The cognitive interview showed that patients were able to paraphrase the items, and considered them relevant and easily understood. CONCLUSION: The tool was translated and cross-culturally adapted to be used in Brazil. The authors believe this translation is suited for validation.

RESUMO INTRODUÇÃO: Pacientes submetidos à radioterapia para tratamento de câncer de cabeça e pescoço apresentam diversos sintomas, com predominância de sintomas orais. O Vanderbilt Head and Neck Symptom Survey version 2.0 é um instrumento americano que foi desenvolvido para avaliar sintomas orais em pacientes com câncer de cabeça e pescoço submetidos à radioterapia. OBJETIVO: Traduzir o Vanderbilt Head and Neck Symptom Survey version 2.0 e adaptá-lo culturalmente para subsequente validação e aplicação no Brasil. MÉTODO: Um método de tradução e adaptação cultural de instrumentos foi utilizado, o qual inclui traduções independentes, síntese das traduções, retrotraduções, comitê de especialistas e pré-teste. O pré-teste foi realizado em 37 pacientes com câncer de cabeça e pescoço divididos em quatro grupos para avaliar a relevância e entendimento dos itens. Dados foram submetidos à análise estatística descritiva. RESULTADOS: A média geral do índice de validade de conteúdo foi 0,79 para as equivalências semânticas e idiomáticas; e maior que 0,8 para as equivalências cultural e conceitual. A entrevista cognitiva mostrou que os pacientes foram capazes de parafrasear os itens e os consideravam relevante e de fácil entendimento. CONCLUSÃO: O instrumento foi traduzido e adaptado culturalmente ao Brasil. Nós acreditamos que esta tradução está apta para a validação.

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.

Translation and cross-cultural adaptation into Brazilian Portuguese of the Vanderbilt Head and Neck Symptom Survey version 2.0 (VHNSS 2.0) for the assessment of oral symptoms in head and neck cancer patients submitted to radiotherapy.

INTRODUCTION: Patients submitted to radiotherapy for the treatment of head and neck cancer have several symptoms, predominantly oral. The Vanderbilt Head and Neck Symptom Survey version 2.0 is an American tool developed to evaluate oral symptoms in head and neck cancer patients submitted to radiotherapy. OBJECTIVE: The aim of the present study was to translate the Vanderbilt Head and Neck Symptom Survey version 2.0 into Brazilian Portuguese and cross-culturally adapt this tool for subsequent validation and application in Brazil. METHODS: A method used for the translation and cultural adaptation of tools, which included independent translations, synthesis of the translations, back-translations, expert committee, and pre-test, was used. The pre-test was performed with 37 head and neck cancer patients, who were divided into four groups, to assess the relevance and understanding of the assessed items. Data were submitted to descriptive statistical analysis. RESULTS: The overall mean of the content validity index was 0.79 for semantic and idiomatic equivalence, and it was higher than 0.8 for cultural and conceptual equivalence. The cognitive interview showed that patients were able to paraphrase the items, and considered them relevant and easily understood. CONCLUSION: The tool was translated and cross-culturally adapted to be used in Brazil. The authors believe this translation is suited for validation.

The Functionality Assessment Flowchart (FAF): a new simple and reliable method to measure performance status with a high percentage of agreement between observers.

BACKGROUND: Performance status (PS) assessment is an integral part of the decision-making process in cancer care. Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) PS are the most widely used tools. In some studies, the absolute agreement rate of these tools between observers has been moderate to low. The present study aimed to evaluate the inter-observer reliability and construct validity of the new Functionality Assessment Flowchart (FAF) and compare it with ECOG PS and KPS in a sample of cancer patients. METHODS: The patients were recruited by convenience from the waiting rooms of the Breast and Gynecology Ambulatory in a cross-sectional study. Two trained medical students (observer A) and five medical oncologists (observers B) independently rated women according to the ECOG PS, KPS and FAF. After the determining the PS scores, observer A administered the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire to the participants. The agreements between observers A and B were investigated using the absolute agreement rate (%), weighted and unweighted kappa and Spearman's correlation test. For construct validity, the PS scores were correlated with functional and fatigue scores by performing correlation analysis. RESULTS: Eighty women with a median age of 57 years were included in the study (86% accrual rate). Among these women, 39 (48.8%) had advanced cancer. The overall absolute agreement rate between observers was 49.4% for KPS, 67% for ECOG PS, and 78.2% for FAF. When using unweighted kappa values, the inter-observer reliability was "fair", "moderate" and "substantial" for KPS, ECOG PS and FAF, respectively. However, when using weighted kappa statistics, "substantial" agreement was observed for KPS and ECOG PS and "nearly perfect" agreement was observed for FAF. All of the PS scales correlated very well with the functional and fatigue scores. CONCLUSIONS: We present a new instrument with moderate to high inter-observer agreement and adequate construct validity to measure PS in cancer patients.

"There won't' be anything else...it's over": perceptions of women referred to palliative care only.

BACKGROUND: It is not well-known how women with advanced breast and gynecological cancers cope with the transition to palliative care (PC) only, but we anticipate that this is a challenging situation for them. OBJECTIVE: To investigate women's understanding on the reasons of anticancer treatment withdrawal, their ideas about PC, and also perceptions of the communication of bad news. METHOD: Twenty women were interviewed by a single researcher after being informed that their antineoplastic treatment would be discontinued and they would be exclusively monitored by PC staff. The interviews were audiotaped, transcribed verbatim, and analyzed according to content analysis. RESULTS: Three categories were identified in the participants' narratives: (1) an understanding of the meaning of PC; (2) a lack of understanding of the shift in treatment and follow-up; (3) differing perspectives about hope. The PC Unit was stigmatized as a place to die, resulting in a "place to die" subcategory. The narratives of the participants who previously had experienced PC converged on a subcategory that reveals better recognition of the importance of the PC Unit as "a place that enhances the quality of life". CONCLUSION: The participants manifested little knowledge about PC and the forthcoming strategies for their clinical follow-up. In addition, the PC Unit was patently stigmatized as a place to die. Early referral to PC seems to be associated with a less painful therapeutic transition, based on more accurate knowledge of the importance of PC.

Quimioterapia neoadjuvante e resposta patológica: coorte retrospectiva / Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

OBJETIVO: Avaliar a taxa de resposta patológica completa atingida pelas pacientes com diagnóstico de câncer de mama localmente avançado submetidas à quimioterapia neoadjuvante baseada no esquema doxorrubicina/ciclofosfamida seguido de paclitaxel. MÉTODOS: Coorte retrospectiva de pacientes admitidas no Hospital de Câncer de Barretos com câncer de mama localmente avançado entre 2006 e 2008 submetidas ao protocolo de doxorrubicina/ciclofosfamida seguido de paclitaxel (4 ciclos de doxorrubicina 60mg/m² e ciclofosfamida 600mg/m² a cada 21 dias; 4 ciclos de paclitaxel 175mg/m² a cada 21 dias). As seguintes variáveis foram avaliadas: idade, menopausa, performance status, estadiamento clínico inicial, dados antropométricos, quimioterapia (dose - duração), perfil de toxicidade, estadiamento clínico pós-tratamento, cirurgia, resposta patológica completa, sobrevida livre de doença e características anatomopatológicas (tipo e grau histológico, perfil hormonal e comprometimento linfonodal). A análise estatística foi realizada considerando-se o nível de significância de 5%. RESULTADOS: Das 434 pacientes avaliadas, 136 foram excluídas por erro no estadiamento ou por terem recebido outro tipo de quimioterapia. A mediana de idade foi 50 anos, todas com performance status 0-1. A mediana do tamanho clínico inicial do tumor foi 65mm e a mediana do tamanho clínico final do tumor foi 22mm. Apresentaram resposta patológica completa 51 (17,1%) pacientes. Aquelas que apresentavam perfil hormonal negativo ou que eram triplo-negativas (Her-2 e perfil hormonal negativos) tiveram impacto favorável na resposta patológica completa. CONCLUSÃO: Quimioterapia neoadjuvante com doxorrubicina/ciclofosfamida seguidas de paclitaxel ofereceu taxa de resposta patológica completa na população estudada de acordo com a literatura. Pacientes triplo-negativas tiveram maior chance de atingir essa resposta.

OBJECTIVE: To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/cyclophosphamide regimen followed by paclitaxel. METHODS: A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m² and cyclophosphamide 600mg/m² every 21 days; 4 cycles of paclitaxel 175mg/m² every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose - duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. RESULTS: Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. CONCLUSION: Neoadjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

Controle de qualidade em rastreamento mamográfico no Brasil: experiência doHospital de Câncer de Barretos / Quality control in mammographic breast cancer screening in Brazil: the Barretos Cancer Hospital experience

O rastreamento mamográfico tem potencial de reduzir o estádio no momento do diagnóstico e, portanto, reduzir a mortalidade por câncer de mama. Cada programa deve estar atrelado a serviços de referência no diagnóstico e no tratamento específico da doença. Os resultados podem ser avaliados conforme indicadores de qualidade, descritos previamente por especialistas, tais como nas orientações da European Breast Cancer Network (EBCN). Parte dos indicadores propostos pela EBCN puderam ser adequadamente analisados nas mulheres com câncer de mama detectado pelo programa de rastreamento mamográfico do Hospital de Câncer de Barretos. A intenção foi detectar falhas, avaliar resultados e propor melhorias ao programa. Alguns desses indicadores, incluindo os relacionados ao diagnóstico, a análise anatomopatológica e o tratamento cirúrgico, foram descritos neste artigo e estiveram alinhados aos recomendados pela EBCN. Isto caracteriza a qualidade de um serviço de mastologia terciário, dedicado no tratamento multidisciplinar do câncer de mama. Entretanto, os intervalos de tempo necessitam ser adaptados à realidade nacional, muito provavelmente, em virtude das características sociais brasileiras. Alguns aspectos principais foram citados, para que futuros programas de rastreamento possam delinear a análise do seu programa de qualidade.

Mammographic screening has the potential to reduce the stage at diagnosis, and thus reduce mortality from breast cancer. Each program should be connected to reference departments in the diagnosis and treatment of breast cancer. The results of a mammographic screening program can be evaluated by means of indicators of quality, previously described by experts such as the guidelines of the European Breast Cancer Network (EBCN). Part of the indicators proposed by EBCN could be properly analyzed in women with breast cancer detected by the mammographic screening program of Barretos Cancer Hospital. The intention was to detect problems, evaluate results, and propose improvements to the program. Some of these indicators, including those related to the diagnosis, pathologic analysis and surgical treatment, are described in this article, and are aligned to the recommended by EBCN. These results reflect the quality of a tertiary breast surgery department dedicated to the multidisciplinary approach of breast cancer. However, the time intervals need to be adapted to the national reality, most likely due to the brazilian social aspects. Some key points were mentioned, in order to assist future screening programs in developing countries to outline the analysis of their quality program.

Neoadjuvant chemotherapy and pathologic response: a retrospective cohort.

OBJECTIVE: To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/cyclophosphamide regimen followed by paclitaxel. METHODS: A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m² and cyclophosphamide 600mg/m² every 21 days; 4 cycles of paclitaxel 175mg/m² every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose - duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. RESULTS: Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. CONCLUSION: Neoadjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.