Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor.

Breast cancer is a leading cause of neoplasia-associated death in women worldwide. Regulatory T (Treg) and Th17 cells are enriched within some tumors, but the role these cells play in invasive ductal carcinoma (IDC) of the breast is unknown. We show that CD25(+) CD4(+) T cells from PBMCs and tumor express high levels of Foxp3, GITR, CTLA-4, and CD103, indicating that tumor-infiltrating Treg cells are functional and possibly recruited by CCL22. Additionally, we observed upregulation of Th17-related molecules (IL-17A, RORC, and CCR6) and IL-17A produced by tumor-infiltrating CD4(+) and CD8(+) T lymphocytes. The angiogenic factors CXCL8, MMP-2, MMP-9, and vascular endothelial growth factor detected within the tumor are possibly induced by IL-17 and indicative of poor disease prognosis. Treg and Th17 cells were synchronically increased in IDC patients, with positive correlation between Foxp3, IL-17A, and RORC expression, and associated with tumor aggressiveness. Therefore, Treg and Th17 cells can affect disease progression by Treg-cell-mediated suppression of the effector T-cell response, as indicated by a decrease in the proliferation of T cells isolated from PBMCs of IDC patients and induction of angiogenic factors by IL-17-producing Th17. The understanding of regulation of the Treg/Th17 axis may result in novel perspectives for the control of invasive tumors.

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination.

BACKGROUND: Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. METHODS: Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. RESULTS: Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. CONCLUSION: Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination.

Conceitos de cinética tumoral aplicados à quimioterapia para o câncer de mama / Concepts of tumoral kinetics applied to chemotherapy of breast cancer

A maioria das pacientes com câncer de mama está sujeita à quimioterapia, e os comprovados benefícios da quimioterapia adjuvante na sobrevida global e livre de doença podem ser explicados pelos conceitos de eliminação celular. A aplicação dos conceitos de eliminação logarítmica de Skipper ao crescimento do câncer de mama humano, o qual parece seguir a cinética gompertziana, sugere que não apenas o uso de drogas sem resistência cruzada seja importante, mas a dose e a intensidade da quimioterapia administrada sejam variáveis clinica mente importantes que podem ser manipuladas para aumentar a sobrevida dos pacientes. Esta revisão da literatura apresenta alguns conceitos teóricos de cinética tumoral importantes para o entendimento de dados empíricos no campo da quimioterapia adjuvante do câncer de mama. A elaboração dos esquemas quimioterápicos é abordada com relação a dose e eficácia dos agentes componentes e quanto ao conceito de intensidade de dose da dose administrada, com aumento das doses e redução dos intervalos entre os ciclos objetivando a otimização, formulando esquemas de alta-dose e dose-denso. A hipótese de Norton-Simon, em que a terapia seqüencial poderia tornar o esquema de administração de agentes citotóxicos dose-densa e que estes esquemas teriam vantagens sobre os esquemas convencionais de administração de drogas também são discutidos.

Most patients who have breast cancer are submitted to chemotherapy, and the proven benefits of adjuvant chemotherapy on disease-free and overall survival in breast cancercan be explained through concepts of cell kill. The application of log-kill concepts of Skipper to human breast cancer growth, which seems to follow Gompertzian kinetics, implies not only theuse of non-cross-resistant drugs is important, but also the dose and the intensity of chemotherapy are clinically important variables which can be used in order to improve disease free survival and overall survival. This literature review presents certain important theoretical concepts of tumoral kinetics in breast cancer therapy. The chemotherapy is scheduled according to the dose and the compounded agent efficiency; and the dose-intensity concept with increasing of the doses and reduction of the breaks between the cycles aiming the optimization, formulating the high-dose and dose-dense schedules. Norton-Simon hypothesis, which supports sequential therapy might makethe administration of cytotoxic agents into dose dense and these schedules would have anadvantage on conventional schedules of drug administration which are also discussed.

Uso da reaçäo em cadeia da polimerase (PCR) para o diagnóstico neonatal de infecçäo perinatal pelo vírus da imunodeficiência humana tipo 1 (HIV) / Use of polimerase chain reaction for neonatal diagnosis of human immunodeficiency virus type 1 (HIV-1) perinatal infection

Com o objetivo de realizar diagnóstico precoce e confiável de infecçäo perinatal pelo HIV-1 no período neonatal, antes do aparecimento de sinais e sintomas de doença, avaliou-se a utilidade da técnica de reaçäo em cadeia da polimerase (PCR) para o HIV-1 em 37 recém-nascidos (idade mediana de 5.5 dias) de mäes infectadas. Das trinta crianças acompanhadas (mediana de 25 meses), 9(30 por cento) eram infectadas. Entre os infectados, 5/9 (56 por cento) tiveram teste PCR neonatal (mediana de 5,5 dias) positivo e em 4/9 (44 por cento) o teste foi negativo. Em nenhuma das 21 crianças näo infectadas o teste foi positivo. Näo se observou associaçäo entre a positividade do teste PCR neonatal e o prognóstico. Apesar de näo identificar todos os casos no período neonatal, este teste é útil para o diagnóstico de infecçäo perinatal e talvez esteja identificando as criançs infectadas pelo HIV-1 durante a gestaçäo

A importancia da mastoplastia reducional reconstrutiva na formaçäo do mastologista / The importance of the reconstructive reduction mammaplasty in the background of the mastologist

O profissional médico que busca especializar-se em Mastologia deve ter um conhecimento global da mama incluindo os aspectos funcionais, nosológicos, psicológicos, sociais, sexuais e estéticos, e esta abordagem completa da mama implica no conhecimento de técnicas cirúrgicas que permitam, preferencialmente, manter as mamas o mais estético possível com funcionalidade. O objetivo deste trabalho é mostrar como essa abordagem é feita, para o aprendizado destas técnicas. Diversas técnicas de abordagem foram utilizadas: Pitanguy (P), Gerardo Peixoto (GP), 5º Pedículo de Liacir Ribeiro (LR), Periareolar a Sampaio Góes (SG). A classificaçao das mamas segundo Bozzola serviu para optarmos por uma ou outra técnica. Foram 26 cirurgias realizadas em pacientes com média de 28 anos de idade. A queixa mais freqüente foi de mamas grandes e dor nas costas. O peso médio retirado foi de 540 g e o maior volume foi de 2.000 g. A maioria das mamas com segmento AM negativo de 0-4 foi operada por técnica de P (15 casos). Houve 2 casos de infecçao. Somente uma paciente teve tecido normal; as demais, alateraçoes fibrocísticas e adenose. O aprendizado de técnicas de mastoplastia reducional permite ao neófito da Mastologia um domínio da abordagem da mama, permitindo-lhe ressecar segmentos mamários quando necessários preservando sua funcionalidade e estética.