Comparison of the performance of four staging systems in determining the prognosis of breast cancer among women undergoing neoadjuvant chemotherapy.

PURPOSE: Different tumor-related factors have been proposed to assess the risk of disease progression and death in women undergoing neoadjuvant breast cancer chemotherapy. Recently, besides the classical pre-treatment clinical stage (CS) and post-treatment pathologic stage (PS), estrogen receptor status and histologic grade (CPS + EG score) and HER2 results (Neo-Bioscore) have also been added to this suite of staging systems, generating new scores. The present study aims to compare the performance of these four staging systems, namely CS, PS, CPS + EG and Neo-Bioscore, in the prognosis of breast cancer in women undergoing neoadjuvant chemotherapy. METHODS: This study comprises a retrospective cohort study of female breast cancer patients diagnosed at the Brazilian National Cancer Institute, Brazil from January 2013 to December 2015. A descriptive analysis of patient characteristics was conducted, and Kaplan-Meier curves, a Cox proportional hazard analysis and Receiver Operating Characteristic (ROC) curves were developed according to the assessed staging system scores. RESULTS: A total of 803 patients were eligible for this study. Most were under 65 years old (88.0%), presented advanced tumors (clinical stage ≥ IIB 77.1%), with positive estrogen receptor (71.2%) and negative HER2 (75.7%) results. During the follow-up, 172 patients (21.4%) evolved to death. A statistical difference (p < 0.001) was observed between 5 year disease-free survival and 5 year overall survival rates according to the PS, CPS + EG and Neo-Bioscore staging systems. CONCLUSION: The PS, CPS + EG and Neo-Bioscore staging systems were proven to be equivalent to predict the prognosis of patients undergoing neoadjuvant chemotherapy.

Post-marketing assessment of generic tamoxifen in Brazilian breast cancer patients.

Generic formulations of tamoxifen are commonly prescribed to oestrogen receptor-positive breast cancer patients at the Brazilian National Cancer Institute (INCA). We carried out a post-marketing surveillance of the generic tamoxifen formulation in current use at INCA, by comparing plasma concentrations of the parent drug and metabolites obtained with the generic vs the reference formulation. Thirty patients participated in an open-label, bracketed protocol, comprising 3 successive phases of 30-32 days each: the generic formulation was used in phases 1 and 3 and the reference formulation in phase 2. Two blood samples were collected in the last 4 days of each phase, for LC-MS/MS quantification of tamoxifen and metabolites in plasma. The median plasma concentrations (ng/mL) for the reference formulation were as follows: tamoxifen, 135.0 (CI 95% 114.2-155.8); endoxifen, 35.3 (30.0-40.8); and 4-hydroxytamoxifen, 4.8 (4.2-5.4). The endoxifen/tamoxifen plasma concentration ratio was 0.27 (0.21-0.25). ANOVA detected no statistically significant difference in plasma concentrations of tamoxifen, metabolites or the endoxifen/tamoxifen ratio among the three phases. The genetic component (rGC) of the CYP2D6-mediated conversion of tamoxifen into endoxifen, estimated using the repeated drug administration procedure across the three phases, was 0.87, pointing to an important component of genetic variability. In conclusion, this first post-marketing surveillance trial of oncologic generic drugs carried out in Brazilian patients verified the switchability between the reference and the generic tamoxifen formulation currently used at our institution. The adopted bracketed protocol adds confidence to this conclusion and may serve as a frame for future trials of post-marketing assessment of other generic drug products.

Impact of Number of Positive Lymph Nodes and Lymph Node Ratio on Survival of Women with Node-Positive Breast Cancer.

OBJECTIVE: This study aimed to evaluate the association of axillary lymph node ratio (LNR) and number of positive lymph nodes (pN) with the risk of breast cancer recurrence and death. MATERIALS AND METHODS: A retrospective cohort study of node-positive stage II and III breast cancer patients diagnosed and treated between 2008 and 2009 at the Brazilian National Cancer Institute (INCA), Brazil. Overall and disease-free survival curves for number of positive lymph nodes (pN) and lymph node ratio (LNR) risk groups were constructed using the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed using stepwise forward Cox regression models. RESULTS: In total, 628 women with node-positive breast cancer were included. Most patients (69.5%) had advanced clinical stage tumors (≥IIB). The median follow-up was 58 months (range: 3-92 months). The adjusted recurrence hazard of pN2 and pN3 patients was 2.47 (95% Confidence Interval [CI] 1.72-3.56) and 2.42 (1.62-3.60), respectively, compared to pN1 patients (p<0.001), while the hazard of intermediate (0.21-0.65) and high-risk (>0.65) LNR was 2.11 (1.49-3.00) and 3.19 (2.12-4.80), respectively, compared to low-risk LNR (≤0.20) patients (p<0.001). On the other hand, the hazard of death of pN2 and pN3 patients was 2.17 (1.42-3.30) and 2.41 (1.53-3.78), respectively (p<0.001), and the hazard of intermediate (0.21-0.65) and high-risk (>0.65) LNR patients was 1.70 (1.13-2.56) and 2.74 (1.75-4.28), respectively (p≤0.001). CONCLUSION: Higher pN and LNR were associated with shorter disease-free survival and overall survival times.

Impact of Treatment Type on Overall Survival in ElderlyBrazilian Women with Breast Cancer

Objective: To analyze the survival of elderly patients with breast cancer according to the type of treatment used. Methods: A cohort study of women aged 80 or over with breast cancer registered with the Brazilian National Cancer Institute (Instituto Nacional do Câncer - INCA) between 2008 and 2009 was conducted. Prognosis was analyzed according to the cancer treatment performed: surgery, radiotherapy, or hormone therapy. Analysis of the overall 5-year survival rate was performed using the Kaplan - Meier method, and comparisons of curves were undertaken using the log-rank test. For multiple regression analysis, Cox regression was used, adjusting for age and clinical stage, considering values of p < 0.05 as significant. Data were all analyzed using the statistical package SPSS version 20. Results: 70 women with a mean age of 84.0 ± 3.7 years at diagnosis participated in the study. The median follow-up time was 37.1 months (range 0.5­75.5), and 31 deaths (44.3%) occurred during this time. The median survival time was 51.2 months (95% CI, 44.9­57.4), higher in those who underwent surgery (p = 0.012) and those who had hormone therapy (p=0.001). Treatment with surgery reduced the risk of death by 61.7% (HR 0.3; 95% CI, 0.1­0.6; p = 0.001) when adjusted for clinical stage and age at diagnosis. However, there was no significant benefit from radiotherapy (HR 1.2; 95% CI, 0.5­2.5; p = 0.694). Conclusion: Treatment with surgery and hormone therapy increased the survival of our Brazilian patients with breast cancer aged 80 or over.

Breast reconstruction and risk of lymphedema after mastectomy: A prospective cohort study with 10 years of follow-up.

OBJECTIVE: The aim of this study is to assess the incidence and risk factors for lymphedema in women submitted to mastectomy, with or without breast reconstruction. METHODS: A cohort study was performed on women submitted to mastectomy with axillary lymphadenectomy in a single center. The follow-up included clinical evaluation and arm column measurements before surgery, at 30 days, 6 months, 5 years, and 10 years after surgery. For women subjected to late reconstruction, the time of occurrence of lymphedema (before or after reconstruction) was observed. RESULTS: We followed up on 622 patients submitted to mastectomy and axillary lymphadenectomy for an average period of 57 months after surgery. In total, 94 women were submitted to breast reconstruction, 47 (8%) of them immediate and 47 (8%) late reconstructions. Incidence of lymphedema in the whole group was 33% (n = 204). Among the patients submitted to reconstruction, 28% of them developed lymphedema, on average, 93 months (CI 95%, 88-98) after surgical treatment. In women not subjected to reconstruction, 179 (34%) developed lymphedema, on average, after 106 months (CI 95%, 96-116) (p = 0.03). Breast reconstruction reduced lymphedema risk in 36% (HR = 0.64, CI 96%, 0.42-0.98, p = 0.04). After adjustment for pathological staging and radiotherapy, this was not statistically significant (HR = 0.79, CI 95%, 0.52-1.21, p = 0.28). CONCLUSION: Breast reconstruction does not increase the risk of lymphedema in long-term follow-up.

Hydrothermal treatment of rough rice: effect of processing conditions on product attributes.

A method involving hydration, tempering and heating steps is presented to process rough rice as alternative to traditional parboiling with pressure steam. The effects of temperature (66-84 °C), tempering time (60-420 min) and heating time (30-180 min) on gelatinization degree and milling yield were analyzed by response surface method (RSM). A maximum value of gelatinization degree (37.0 %) and milling yield of 67.7 % were reached with a process temperature of 84 °C using tempering and heating times of 178 and 104 min respectively. A slight reduction of crystallinity (14 %) and a significant improvement of nutritional value with increments of 150 and 60 % in riboflavin and calcium contents were obtained in comparison with control (untreated rice). Hardness and adhesiveness of processed rice were intermediate between those of control and completely gelatinized rice. The proposed method, with lower temperature requirements than traditional parboiling, is presented to obtain an alternative product, expanding consumer choices.

Margens cirúrgicas no tratamento conservador do câncer de mama:revisão sistemática / Surgical margins in conservative treatment of breast cancer: systematic review

Há um intenso debate sobre margens cirúrgicas, embora o Consenso Internacional de 2010 defina margem positiva como tumor microscópico tocando o nanquim e margem de 2 mm para carcinoma in situ. No Instituto Nacional de Câncer, considerou-se adequada a margem de 10 mm para pacientes submetidas à cirurgia conservadora, e a reexcisão foi recomendada para aquelas menores que 10 mm. Buscamos referências bibliográficas no banco de dados MEDLINE que estudassem a taxa de ampliações de margens cirúrgicas e neoplasia residual, além da associação entre margens e recidiva de câncer de mama nas pacientes submetidas a tratamento conservador. Identificamos 113 artigos, porém apenas 5 foram incluídos. Encontramos apenas 2 artigos que associaram taxa de ampliação e neoplasia residual nas peças de reexcisão. Os demais artigos incluídos avaliaram o impacto das margens cirúrgicas na recorrência local e a distância e na sobrevida global. A presença de doença residual na peça de ampliação demonstrou-se importante fator prognóstico e correlaciona-se com o risco de doença acdistância, demonstrando que o componente biológico do tumor é mais importante do que a distância das margens.

There is an extensive debate about surgical margins, although 2010 International Consensus defines positive margin as microscopic tumor touching the stain and 2 mm for in situ carcinoma. At INCA, is considered satisfactory 10 mm margin for patients undergoing conservative surgery, and reexcision is recommended for those smaller than 10 mm. We searched for references at MEDLINE that studied reexcision rates and residual disease, and the association between surgical margins and breast cancer relapse between patients treated with conservative surgery. An amount of 113 articles were identified, but only 5 included. Only 2 articles associated reexcision rates and residual disease in reexcision specimens. The others evaluated the impact of surgical margins in local and distance recurrence and global survival. Residual disease in reexcision specimens was an important prognostic factor and correlates to the risk of distant recurrence, showing that the biologic component of the tumor might be more important than margins distance.

Análise estatística espacial da mortalidade por câncer de mama feminina no estado do Rio de Janeiro, 2001 a 2006 / Spatial statistical analysis of mortality from breast cancer women in the state of Rio de Janeiro, 2001-2006

Objetivos: Avaliar a existência de dependência espacial na taxa de mortalidade por câncer de mama feminino no Estado do Rio de Janeiro, no perí­odo de 2001 a 2006 e possíveis variáveis explicativas. Material e métodos: Análise da correlação espacial da taxa de mortalidade por câncer de mama nos triênios 2001 a 2003 e 2004 a 2006, através do calculo do I global de Moran, tendo como variáveis explicativas: a idade, a raça, o estado civil, o ní­vel educacional, a renda médio do trabalho principal das pessoas adultas de cada municí­pio, o Í­ndice de mamógrafos por municí­pio, o Índice de Desenvolvimento Humano Municipal, Índice Firjan de Desenvolvimento Municipal, a cobertura da população por saúde complementar, a média de consultas nas especialidades básicas e a despesa municipal de saúde por habitante. Foi utilizado o método proposto por Andrade e Szwarcwald para estabelecer a distribuição espacial da taxa de mortalidade por câncer demama feminino e identificar os principais fatores responsáveis pela variação espacial. Resultados: A dependência espacial foi constatada pelos resultados da análise estatística para taxa de mortalidade do triênio 2001 a 2003 (...). As variáveis que melhor explicaram os aglomerados espaciais foram o Valor do rendimento médio do trabalho principal das pessoas adultas e o Índice de mamógrafos por município. Conclusão: Ocorreu dependência espacial na taxa de mortalidade por câncer de mama feminina no perí­odo de 2001 a 2003, sendo que esta pode ser explicada, em parte, pelo rendimento médio dos habitantes e pelo Í­ndice de mamógrafos de cada municí­pio...

Objectives: To analyze the existence of spatial dependence in the mortality rate for female breast cancer in the State of Rio de Janeiro in the period 2001-2006 and possible explanatory variables. Methodology: Analysis of the spatial correlation of mortality rate from breast cancer in two triennium 2001 to 2003 and 2004 to 2006. To evaluate thespatial dependence was calculated the Global Moran's Index and being used as explanatory variables: age, race, marital status, educational level, the average income for adult peoplefrom the main job (per municipality), the rate of mammography unit by municipality, the Municipal Human Development Index, the Firjan´s Index Municipal Development, the percentage of population covered by private health insurance system, the average numberof basic care medical visits and total spending per person, per year, on health by the municipal government. It was used the method propose by Andrade and Szwarcwald aiming to establish the spatial mortality rate caused by female breast cancer and recognize the main aspects of this spatial variation. Results: The spatial dependence was found intriennium 2001-2003 (Moran I statistic standard deviate = 1,7379, p=0,0410), but the same result were not found during 2004-2006 (Moran I statistic standard deviate =0,4450, p=0,3281). The best variable that explains spatial clusters was “the average income for adult people from the main job” and “the rate of mammography unit by municipality”. Conclusion: It was detected during 2001-2003 a spatial dependence in death rate by femalebreast cancer . This result may be partly explained by average income per inhabitant and the rate of mammography unit by municipality.

Lymphoscintigraphy in breast cancer: a short review about the impact on upper limb after surgical treatment

Breast cancer is still associated with high mortality rates and one of the most important factors governing long survival is accurate and early diagnosis. In underdeveloped countries, this disease frequently is only detected in advanced stages; however, through mammography, many women have been diagnosed at early stages. In this context, the sentinel lymph node (SLN) technique is associated with less postoperative morbidity compared to axillary lymphadenectomy. Lymphoscintigraphy has emerged as a method for the evaluation of lymphatic drainage chains in various tumours, being both accurate and non invasive. The aim of this work is to present the main aspects which cause controversy about SLN and lymphoscintigraphy and the impact that these procedures have had on lymphedema after surgical treatment for breast cancer. A short review including papers in English, Spanish and Portuguese, available on Lilacs and Medline database, published between January, 2000 and July, 2008 was performed. The key words breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema were used. Various studies have aimed to compare the incidence and prevalence of lymphedema according to the technique used; however, the population subjected to SLN is different from the one with indication for axillary lymphadenectomy regarding staging. Moreover, little is known about long term morbidity since it is a relatively new technique. In conclusion, the development of surgical techniques has permitted to minimize deformities and the current trend is that these techniques be as conservative as possible. Thus, lymphoscintigraphy plays an important role in the identification of SLN, contributing to the prevention and minimization of postoperative complications.

O câncer de mama é ainda associado com altas taxas de mortalidade e um dos mais importantes fatores de manutenção de longa sobrevivência é a precisão e o diagnóstico precoce. Em países em desenvolvimento, essa doença freqüentemente é apenas detectada em estágios avançados. Entretanto, através da mamografia, muitas mulheres tiveram o diagnóstico em estágios precoces. Nesse contexto, a técnica do linfonodo sentinela (LNS) está associada com a menor morbidade pós-operatória comparada a linfadenectomia axilar. A linfocintilografia tem emergido como um método para a avaliação das cadeias de drenagem linfática em vários tumores, sendo precisa e não invasiva. O objetivo desse trabalho é apresentar os principais aspectos os quais causam controvérsia sobre LNS e a linfocintilografia e o impacto que esses procedimentos tem tido no linfedema após tratamento cirúrgico para câncer de mama. Uma breve revisão incluindo artigos em inglês, espanhol e português, disponíveis no Lilacs e no Medline, publicados entre janeiro de 2000 e julho de 2008, foi realizada. As palavras-chaves breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema foram usadas. Vários estudos têm objetivado comparar a incidência e prevalência do linfedema de acordo com as técnicas usadas. Entretanto, a população sujeita a LNS é diferente daquela com indicação para linfedenectomia axilar relacionada com o estadiamento. Pouco é conhecido sobre morbidade em longo prazo, uma vez que a técnica é relativamente nova. Concluindo, o desenvolvimento de técnicas cirúrgicas tem permitido minimizar deformidades e a corrente tendência é que essas técnicas sejam tanto conservativas quanto possível. Assim, a linfocintilografia tem papel importante na identificação de LNS, contribuindo para a prevenção e minimização de complicações pós-operatórias.