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SUMMARY OBJECTIVE: Tumor-infiltrating lymphocytes are detectable in up to 75% of triple-negative breast cancer. The composition of these infiltrates may influence prognosis and is not known regarding regulatory or effector lymphocytes. The objectives of this study were to describe and quantify the composition of the tumor-infiltrating lymphocytes before and after chemotherapy (neoadjuvant chemotherapy) and to evaluate their association with complete pathological response and overall survival. METHODS: This was a retrospective observational study. Clinical and pathological data from 38 triple-negative breast cancer patients treated with neoadjuvant chemotherapy at the University Hospital (HUCFF/UFRJ), between November 2004 and November 2018, were analyzed. The Stromal tumor-infiltrating lymphocytes (Stromal tumor-infiltrating lymphocytes) have been identified on hematoxylin and eosin-stained sections according to the guidelines of the "International tumor-infiltrating lymphocytes Working Group." Immunohistochemistry studies were performed to identify T-cell subsets (i.e., CD3, CD4, CD8, and FOXP3) and T-cell exhaustion (i.e., programmed cell death protein 1). RESULTS: Statistically significant changes in stromal tumor-infiltrating lymphocyte categories were observed before and post-neoadjuvant chemotherapy, with 32% of intermediate cases becoming high. The correlation between pre-neoadjuvant chemotherapy stromal tumor-infiltrating lymphocytes and pathological response, pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy, and stromal tumor-infiltrating lymphocytes and overall survival was not statistically significant. However, we noticed an increase of cells that favor the antitumor activity (i.e., CD3, CD8, and CD8/FOXP3 ratio) and decreased levels of cells inhibiting tumor activities (i.e., FOXP3 and programmed cell death protein 1) post-neoadjuvant chemotherapy. Importantly, programmed cell death protein 1 expression pre-neoadjuvant chemotherapy showed an association with pathological response. CONCLUSION: In this study, we observed that chemotherapy significantly increases stromal tumor-infiltrating lymphocytes, CD8 T cells, as well as CD8/FoxP3 ratio. Most importantly, programmed cell death protein 1 expression before neoadjuvant chemotherapy positively correlates with pathological response suggesting the use of programmed cell death protein 1 as a prognostic marker before neoadjuvant chemotherapy.
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SUMMARY OBJECTIVE: This study aimed to determine the frequencies of Epstein-Barr virus, types 1 and 2 infection, and 30 bp del-latent membrane protein 1 viral polymorphism in gastric adenocarcinomas, as well as to investigate the association between Epstein-Barr virus infection and tumor location, type, and the patient's sex. METHODS: Samples were collected from 38 patients treated at a university hospital in Rio de Janeiro, Brazil. Epstein-Barr virus detection and genotyping were performed by polymerase chain reaction, followed by polyacrylamide gel electrophoresis and staining by the silver nitrate method. RESULTS: Overall, 68.4% of patients had Epstein-Barr virus-positive tumors. Of these, 65.4% presented infection by Epstein-Barr virus type 1, 23.1% by Epstein-Barr virus type 2, and 11.5% had coinfection with types 1 and 2. The 30 bp del-latent membrane protein 1 polymorphism was found in 42.3% of Epstein-Barr virus-positive tumors, 23.1% had the wild-type virus, and 23.1% had the wild-type and the polymorphism concomitantly. In 11.5% of Epstein-Barr virus-positive tumors, it was impossible to determine whether there was polymorphism or not. Tumor location in the antrum (22 of 38) and diffuse type (27 of 38) were predominant. There was no significant difference in Epstein-Barr virus infection or the 30 bp del-latent membrane protein 1 polymorphism between men and women. CONCLUSION: Epstein-Barr virus infection was found in 68.4% of tumors investigated in this study. To the best of our knowledge, this is the first article showing the coinfection of Epstein-Barr virus types 1 and 2 in gastric carcinoma in Brazil.
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Introduction: The objective of this study is to describe the profile of patients from a public institution, submitted to neoadjuvant chemotherapy (NACT), comparing the verified pathological response with literature data. Methods: Observational retrospective cohort study on breast cancer patients diagnosed between September 2001 and October 2018 and treated with NACT at Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ), located in Rio de Janeiro, Brazil. The adopted neoadjuvant chemotherapy regimen was based on anthracycline and docetaxel. Results: A total of 133 patients were evaluated. The average age in this group was 54 years (28-86), 49 women (37%) were under 50 years old. The following distribution by molecular subtype was observed: overexpression or amplification of the human epidermal growth factor receptor 2 (HER2+) (13 women, 26.6%), Luminal (19 women, 38.8%), and Triple-negative (TN) (17 women, 34.6%). The HER2+ and TN subtypes had a higher incidence of cases between 40-49 years and 50-59 years. As for the initial staging, 34% were IIIA; 26%, IIB; and 19%, IIIB. Only one patient did not undergo surgery after NACT, 33 (24.8%) underwent conservative surgery, and 99 patients (74.4%) underwent mastectomy. Regarding the axillary approach, 41 (31%) underwent sentinel lymph node biopsy and 88 (66%) had an indication for lymphadenectomy. In the anatomopathological evaluation of the surgery, 12 (9.1%) patients obtained a pathologic complete response (pCR) and 113 (84.9%), partial or no response to chemotherapy. Conclusion: This research enabled the identification of clinicopathologic characteristics and outcome of patients who received neoadjuvant chemotherapy in a public university service. The predominance of advanced tumors was observed, stressing the need for public health policies for the screening of breast cancer as well as the guarantee of timely treatment for diagnosed cases. The data somewhat reflect the difficulty that the public sector encounters to carry out the most appropriate treatment. The authors expect that this article, by analyzing the profile and the adopted treatment in real-life cases and in a public university institution, can contribute to the improvement of breast cancer treatment in Brazil.
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Introdução: O câncer de mama é a neoplasia mais incidente no sexo feminino com 48.930 novos casos estimados em 2006, no Brasil. Os principais sítios de metástases são: ossos, pele, linfonodos, pulmões, pleura, fígado ecérebro. Metástases gástricas são raras e pouco citadas na literatura, sendo o câncer de mama o segundo principalresponsável. À endoscopia digestiva alta, apresentam-se mais comumente sob a forma de infiltração intramural difusa, assemelhando-se à linite plástica, e predominam em tumores do tipo lobular. A comparação histológica dos espécimes é obrigatória, porém a imunoistoquímica também pode ser útil. O prognóstico é ruim, visto que adoença metastática raramente se restringe ao estômago. O tratamento é paliativo e inclui quimioterapia, terapia hormonal e radioterapia. Relato de caso: Paciente com câncer de mama em tratamento adjuvante com anastrozol apresentou-se ao serviço com queixa de plenitude gástrica e emagrecimento. Havia massa endurecida em epigástrio,dolorosa à palpação profunda. Ao exame endoscópico, observou-se lesão infiltrante, comprometendo o fundo e metade proximal do corpo gástrico. Foi verificado carcinoma ductal com áreas secretoras de muco e células em anel de sinete metastático para o estômago; CK7 positivo, CK20 e receptor hormonal negativos. Sem evidência de doença em outros focos, a paciente foi tratada com seis ciclos de docetaxel, obtendo-se resposta patológica gástrica completa. Discussão: Apesar de rara, a metástase gástrica é causa de considerável morbidade em pacientes com câncer de mama e pode responder ao tratamento sistêmico apropriado.
Subject(s)
Female , Middle Aged , Humans , Carcinoma, Ductal, Breast/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/secondary , Neoplasm Metastasis , Breast Neoplasms/pathology , PrognosisABSTRACT
De acordo com dados do Instituto Nacional de Câncer do Brasil, quase 30% dos pacientes novos com câncer de mama apresentam no momento do diagnóstico, tumor localmente avançado, inoperável, sendo necessário tratamento primário com quimioterapia. Usualmente esquemas baseados em antraciclinas são efetivos, porém cerca de 30% dos tumores não responderão. Para estes pacientes ainda não existe uma segunda linha de tratamento estabelecida. Objetivo: Avaliar eficácia e toxicidade de radioterapia e capecitabina como segunda linha neo-adjuvante. Pacientes e Métodos: Vinte e oito pacientes com câncer de mama localmente avançados, refratários à quimioterapia primária com antraciclinas, foram estudados entre janeiro de 2003 e maio de 2004. Os pacientes receberam radioterapia (50Gy) e capecitabina (850mg/m2) duas vezes ao dia por 14 dias cada 3 semanas. Resultados: Vinte três de 28 pacientes (82%) tornaram se operáveis. Cinco pacientes não realizaram a cirurgia por progressão de doença. A mediana do tamanho do tumor por avaliação clínica reduziu de 80 cm² para 49cm². Doença residual microscópica foi observada em 3 pacientes (13%) e resposta patológica completa em um paciente. A mediana de linfonodos acometidos foi de dois. O tratamento foi bem tolerado, sem eventos grau 3 ou 4. Conclusão: Nossos resultados indicam que o tratamento de segunda linha neo-adjuvante com radioterapia e capecitabina em pacientes com câncer de mama localmente avançado e refratários a quimioterapia primária com antraciclinas, foi eficaz e bem tolerado. Estudo randomizado e prospectivo comparando radioterapia isolada e capecitabina combinada com radioterapia deverá ser realizado
According to data from Brazils National Cancer Institute, nearly 30% of the new patients who present with breast cancer have locally advanced disease. These patients are inoperable, and tumor reduction is usually attempted with chemotherapy. Firstline anthracyclin-based neoadjuvant chemotherapy is often effective, but about 30% of the patients fail. For those, there is yet no established second-line treatment. Objectives: We have studied the concomitant use of radiation therapy and capecitabine in this setting, in order to determine the toxicity and efficacy of this regimen as a second-line neoadjuvant treatment. Methods: Twenty-eight patients with inoperable locally advanced breast cancer refractory to first-line anthracycline based treatment were enrolled between January 2003 and May 2004. Patients received radiation therapy (50Gy) and concomitant capecitabine (850mg/m²) for 14 days every 3 weeks. Results: This treatment rendered 23 of the 28 patients (82%) operable. The five remaining patients did not undergo surgery due to disease progression. The median clinical tumor size decreased from 80 cm2 to 49 cm2. Microscopic residual disease was observed in 3 patients (13%), and another patient achieved a complete pathologic response. The median number of involved lymph nodes was two. Treatment was well tolerated, with no grade 3 or 4 events. Conclusion: Our data indicate that second-line neoadjuvant treatment with radiation therapy and capecitabine is feasible, well tolerated and effective in patients with locally advanced breast cancer refractory to primary anthracycline-based treatment. These results suggest that a randomized study should be done to compare radiotherapy alone to capecitabine combined with radiotherapy