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Introduction: Mutations in the ESR1 gene (ESR1m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive (ER+) metastatic breast cancer and have been studied as a potential therapeutic target, as well as a predictive and prognostic biomarker. Nonetheless, the role of ESR1m as a possible mechanism of primary endocrine resistance, as well as whether it also occurs in tumors that are resistant to ET administered in early-stage disease as (neo)adjuvant, has not been adequately studied. In this study, we evaluated the prevalence of ESR1m in tumor samples from patients with ER+ breast cancer resistant to neoadjuvant aromatase inhibitor therapy. Methods: We followed a prospective cohort of patients with ER+ HER2- stages II and III breast cancer treated with neoadjuvant endocrine therapy (NET). Tumor samples from patients with a pattern of primary endocrine resistance [defined as a Preoperative Endocrine Prognostic Index (PEPI) score of ≥4] were identified and analyzed for the presence of ESR1m. Results: One hundred twenty-seven patients were included in the cohort, of which 100 (79%) had completed NET and underwent surgery. Among these patients, the PEPI score ranged from 0 to 3 in 70% (70/100), whereas 30% (30/100) had a PEPI score of 4 or more. Twenty-three of these patients were included in the analysis. ESR1 mutations were not identified in any of the 23 patients with early-stage ER+ breast cancer resistant to NET. Discussion: Growing evidence supports the notion that there are different mechanisms for primary and secondary endocrine resistance. Our study suggests that ESR1 mutations do not evolve rapidly and do not represent a common mechanism of primary endocrine resistance in the neoadjuvant setting. Therefore, ESR1m should be considered a mechanism of acquired endocrine resistance in the context of advanced disease. Further research should be conducted to identify factors associated with intrinsic resistance to ET.
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Mutations in the ESR1 gene (ESR1m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive advanced breast cancer and have been recognized as a prognostic and predictive biomarker as well as a potential therapeutic target. However, the prevalence of ESR1m in real-world patients has not been adequately described. Therefore, we sought to evaluate the prevalence of ESR1m in metastatic samples from Brazilian patients with estrogen receptor-positive (ER+) advanced breast cancer previously treated with endocrine therapy. The presence of ESR1m was evaluated in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue using real-time quantitative polymerase chain reaction (RT-qPCR). Mutations in codons 380, 537, and 538 of the ESR1 gene were analyzed. Out of 77 breast cancer samples, 11 (14.3%) showed mutations in the ESR1 gene. ESR1m were detected in a variety of organs, and the D538G substitution was the most common mutation. In visceral metastasis, ESR1m were detected in 25% (8/32) of the samples, whereas in nonvisceral metastasis, ESR1m were detected in 6.7% (3/45) of the samples. The odds of a sample with visceral metastasis having an ESR1 mutation is 4.66 times the odds of a sample of nonvisceral metastasis having an ESR1 mutation (95% CI: 1.13-19.27; p value = 0.0333). Our study indicates that the prevalence of ESR1m in samples from Brazilian patients with metastatic ER+ breast cancer is similar to that described in patients included in clinical trials. We observed an association of ESR1m with visceral metastasis.
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Objective: Triple negative breast cancer (TNBC) is a subset of tumors with an aggressive intrinsic biology, resulting in poor prognosis. Androgen receptor (AR) is currently one of the most studied biomarkers in TNBC, playing a role in the genesis and development of breast cancer. Methods: In this cross-sectional study, we retrospectively reviewed the medical records of all patients with TNBC who received care from 2012 to 2014 at a single health center in southern Brazil. Histological material from breast tumors was analyzed by immunohistochemistry for AR expression and related to age, histological grade, tumor-infiltrating lymphocytes (TILs), and Ki-67. Results: Of 34 TNBC cases identified, 23 (67.6%) were AR negative and 11 (32.4%) were AR positive. The average age of the patients was 51.9 years (range: 3082 years). Among positive cases, AR was weakly expressed in 6 and strongly expressed in 5 cases. Most patients (n=28; 82.0%) had poorly differentiated tumors. Mean Ki-67 expression was 65.0% in AR-negative and 43.6% in AR-positive cases (p<0.05). There was a significant association between age and AR expression (p<0.005), which was associated with mean age 70.8 years in the strongly AR-positive group and 42.3 years in the weakly AR-positive group. The mean percentage of TILs was 38.6% in AR-positive and 39.1% in AR-negative cases (p=0.391). Conclusion: There was no significant association between AR expression and histological grade or TILs. AR positivity in TNBC was associated with older age and tumors with lower Ki-67 expression, indicating two subgroups with distinct phenotypes in patients with TNBC.
Objetivo: O câncer de mama negativo triplo (triple negative breast cancer TNBC) é um subtipo de tumores com biologia intrínseca agressiva, resultando em pior prognóstico. O receptor de andrógeno (androgen receptor AR) é atualmente um dos biomarcadores mais estudados em TNBC, desempenhando papel na gênese e no desenvolvimento do câncer de mama. Métodos: Neste estudo transversal, revisamos retrospectivamente os registros médicos de todos os pacientes com TNBC que receberam atendimento de 2012 a 2014 em um único centro no sul do Brasil. O material histológico dos tumores de mama foi analisado por imuno-histoquímica para a expressão de AR e relacionado a idade, grau histológico, linfócitos infiltrantes de tumores (TILs) e Ki-67. Resultados: Dos 34 casos identificados de TNBC, 23 (67,6%) eram AR negativos e 11 (32,4%), AR positivos. A idade média foi de 51,9 anos (3082 anos). Entre os casos positivos, AR foi fracamente expresso em 6 e fortemente expresso em 5 casos. A maioria dos pacientes (n=28, 82,0%) apresentou tumores pouco diferenciados. A expressão média de Ki-67 foi de 65,0% em AR-negativo e 43,6% em AR-positivo (p<0,05). Houve associação significativa entre a idade e a expressão de AR (p<0,005), associada à idade média de 70,8 anos no grupo com AR fortemente positivo e de 42,3 anos no grupo com AR fracamente positivo. A porcentagem média de TILs foi de 38,6% em AR-positivo e de 39,1% em AR-negativo (p=0,391). Não houve associação significativa entre expressão AR e grau histológico ou TILs. Conclusão: A positividade de AR em TNBC foi associada com idade mais avançada e tumores com menor expressão de Ki-67, indicando dois subgrupos com fenótipos distintos em pacientes com TNBC.
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O angiomiolipoma, tumor mesenquimal benigno, ocorre com mais frequência no rim, sendo que apenas 5 a 10% têm como localização o fígado. É composto por vasos sanguíneos, tecido adiposo e músculo liso. Em 60% dos pacientes, a lesão é assintomática, sendo comumente um achado ocasional em exames de imagem. Quando sintomas estão presentes, estes são: desconforto abdominal, massa palpável no hipocôndrio direito e mal- estar. O angiomiolipoma de fígado é um tumor de difícil diagnóstico, sendo confirmado somente após a análise anatomopatológica. Tem a sua importância como diagnóstico diferencial de outras neoplasias mais comuns, especialmente o carcinoma hepatocelular. O caso relatado chama a atenção para esta condição e compara os achados com os descritos na literatura.
The angiomyolipoma, a benign mesenchymal tumor, occurs most frequently in the kidney, with only 5-10% appearing in the liver. It is composed of blood vessels, adipose tissue and smooth muscle. In 60% of patients the lesion is asymptomatic and is usually a chance finding in imaging studies. If present, symptoms are: abdominal discomfort, palpable mass in the right hypochondrium, and malaise. Angiomyolipoma of the liver is a tumor of difficult diagnosis, which is confirmed only after a histopathological analysis. It is important as a differential diagnosis of other more common malignancies, especially hepatocellular carcinoma. The reported case draws attention to this condition and compares the findings with those described in the literature.
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Humanos , Feminino , Angiomiolipoma , Neoplasias HepáticasRESUMO
Uma paciente de 40 anos apresentou nódulo na mama direita, tendo sido diagnosticado um sarcoma granulocítico. A paciente recusou o tratamento indicado, reingressando no hospital um ano após com tumor de intestino, diagnosticado em outro serviço como linfoma Malt. O diagnóstico diferencial de sarcoma granulocítico com esta e outras neoplasias é fundamental para a indicaçäo de uma terapêutica adequada