Molecular subtypes as a prognostic breast cancer factor in women users of the São Paulo public health system, Brazil.

OBJECTIVE: This study aimed to analyze the prognosis of women with breast cancer by molecular subtypes, sociodemographic variables, and clinical and treatment characteristics. METHODS: This hospital-based retrospective cohort study analyzed 1,654 women over 18 years of age diagnosed with invasive breast cancer from 2000 to 2018. Data were extracted from Brazil's Oncocenter Foundation of São Paulo. The variables analyzed were age, histology, molecular subtypes, clinical staging, treatment type, and diagnosis-to-treatment time. Cox regression analysis was applied to estimate death risk. RESULTS: Women with HER-2-positive (nonluminal) and triple-negative molecular subtypes were more than twice more likely to be at risk of death, with adjusted hazard ratio - HRadj=2.30 (95% confidence interval - 95%CI 1.34-3.94) and HRadj=2.51 (95%CI 1.61-3.92), respectively. A delayed treatment associated with an advanced clinical stage at diagnosis increased fourfold the risk of death (HRadj=4.20 (95%CI 2.36-7.49). CONCLUSION: In summary, besides that interaction between advanced clinical stage and longer time between diagnosis and treatment, HER-2-positive (nonluminal) and triple-negative phenotypes were associated with a worse prognosis. Therefore, actions to reduce barriers in diagnosis and treatment can provide better outcome, even in aggressive phenotypes.

Meningeal carcinomatosis in breast cancer: prognostic factors and outcome.

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

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.

Molecular subtypes as a prognostic breast cancer factor in women users of the São Paulo public health system, Brazil / Subtipos moleculares como fator prognóstico do câncer de mama em mulheres usuárias do sistema público de saúde de São Paulo, Brasil

ABSTRACT Objective: This study aimed to analyze the prognosis of women with breast cancer by molecular subtypes, sociodemographic variables, and clinical and treatment characteristics. Methods: This hospital-based retrospective cohort study analyzed 1,654 women over 18 years of age diagnosed with invasive breast cancer from 2000 to 2018. Data were extracted from Brazil's Oncocenter Foundation of São Paulo. The variables analyzed were age, histology, molecular subtypes, clinical staging, treatment type, and diagnosis-to-treatment time. Cox regression analysis was applied to estimate death risk. Results: Women with HER-2-positive (nonluminal) and triple-negative molecular subtypes were more than twice more likely to be at risk of death, with adjusted hazard ratio — HRadj=2.30 (95% confidence interval — 95%CI 1.34-3.94) and HRadj=2.51 (95%CI 1.61-3.92), respectively. A delayed treatment associated with an advanced clinical stage at diagnosis increased fourfold the risk of death (HRadj=4.20 (95%CI 2.36-7.49). Conclusion: In summary, besides that interaction between advanced clinical stage and longer time between diagnosis and treatment, HER-2-positive (nonluminal) and triple-negative phenotypes were associated with a worse prognosis. Therefore, actions to reduce barriers in diagnosis and treatment can provide better outcome, even in aggressive phenotypes.

RESUMO Objetivo: O objetivo deste estudo foi analisar o prognóstico de mulheres com câncer de mama de acordo com os subtipos moleculares, variáveis sociodemográficas, características clínicas e de tratamento. Métodos: Este foi um estudo de coorte retrospectivo de base hospitalar. Foram analisadas 1.654 mulheres maiores de 18 anos diagnosticadas com câncer de mama invasivo entre 2000 a 2018. Os dados foram extraídos da Fundação Oncocentro de São Paulo, Brasil. As variáveis analisadas foram idade, histologia, subtipo moleculares, estadiamento clínico, tipo de tratamento e tempo entre o diagnóstico e tratamento. A análise de regressão de Cox foi aplicada para estimar o risco de morte. Resultados: As mulheres que apresentaram os subtipos moleculares HER-2-positivo (não luminal) e triplo negativo tiveram risco de morte quase duas vezes maior respectivamente, com razão de risco ajustada — HRaj=2,30 (intervalo de confiança de 95% — 95%IC 1,34-3,94) e HRaj=2,51 (95%IC 1,61-3,92). O atraso no tratamento associado ao avanço do estadiamento clínico ao diagnóstico aumentou em quatro vezes o risco de morte (HRaj=4,20 (IC95% 2,36-7,49). Conclusão: Os fenótipos HER-2-positivo (não luminal) e triplo negativo, além da interação entre estágio clínico avançado e maior tempo entre o diagnóstico e o tratamento, associaram-se a pior prognóstico. Assim, ações para reduzir as barreiras no diagnóstico e tratamento podem proporcionar melhores resultados, mesmo em fenótipos agressivos.

Prolonged time to progression with fulvestrant for metastatic breast cancer.

Although the incidence of breast cancer has been declining in recent years, the disease is still one of the leading causes of cancer deaths in women. Recently, breast cancer has been treated with innovative approaches that use hormone-sensitive therapies. This is because in at least one-third of breast cancers, estrogens mediated via the estrogen receptor pathway act as endocrine growth factors. Fulvestrant has been studied as both first- and second-line therapy for locally advanced and metastatic breast cancer, but few studies have shown its effect as third-line therapy alone. To observe the disease time to progression (TTP) obtained with fulvestrant when used on metastatic breast cancer as first-, second-, and also third-line therapy. We also aimed to correlate the TTP obtained with fulvestrant with hormone receptor, HER2 expression, and metastatic site. This was a cohort study that retrospectively examined medical records of 73 postmenopausal women with advanced breast cancer who were treated with fulvestrant (250 mg/month i.m. injection) and followed at the Department of Medical Oncology at Hospital do Cancer A. C. Camargo in São Paulo, Brazil from August 2003 to December 2006. The median TTP with fulvestrant was about 11 months. When used as the first-line therapy, TTP was about 13 months; when used as second-line, TTP was about 6 months; and when used as third-line, it was about 12 months. No statistically significant difference was observed regarding the therapy line. In patients with positive ER tumors, TTP was 11 months. No significant difference in TTP was observed in negative ER tumors (TTP = 10 months). In patients with positive PgR tumors, TTP was 13 months and for negative PgR, TTP was 6 months (P = 0.008). According to the HER2 status, the TTP was 5 months for HER2+ and 10 months for HER2-. Our findings indicate that fulvestrant is an effective alternative for treatment of metastatic breast cancer.

Meningeal carcinomatosis in solid tumors.

The involvement of the leptomeninges by metastatic tumors can be observed in solid tumors, in which case it is termed meningeal carcinomatosis (MC), and in lymphoproliferative malignant disease. It is more common in breast and lung cancer, as well as melanoma, with adenocarcinoma being the most frequent histological type. MC is usually a late event, with disseminated and progressive disease already present and, it is characterized by multifocal neurological signs and symptoms. Diagnosis is based on the evaluation of clinical presentation, cerebrospinal fluid and neuroimaging studies. The better systemic disease control is observed with new therapeutic agents, and the development of neuroimaging methods is responsible for the increasing incidence of such metastatic evolution. Intrathecal chemotherapy is generally the treatment of choice, although frequently palliative. Prognosis is guarded, although a higher performance status may indicate a subgroup of patients with a more favorable outcome.

Tuberculosis in a patient on temozolomide: a case report.

Temozolomide (TMZ) is a cytotoxic agent of the imidazotetrazine class, chemically related to dacarbazine. Its use poses higher risks of lymphopenia and opportunistic infections. Prophylaxis for Pneumocystis jiroveci must be considered up to 12 months after treatment discontinuation. The due literature (MEDLINE) makes no mention of a possible connection between the use of TMZ and tuberculosis (TB). A female patient, aged 59, featuring glioblastoma multiforme and having undergone solely a brain biopsy, was submitted to TMZ along with radiotherapy. After the first TMZ maintenance cycle, the referred patient was admitted displaying a background of a 40-day afternoon fever and productive coughing. She was thus submitted to a bronchoscopy and LBA, which resulted BAAR 1+/4+. TMZ was then suspended, and rifampicin, isoniazid, and pyrazinamide introduced. Considerations on prophylaxis with isoniazide in cancer patients are long-lived and scarce. Some subgroups are likely to benefit from the prophylactic administration of isoniazide during TMZ treatment, such as those patients under high doses of corticoids, patients with past medical history of TB, the malnourished, patients from endemic regions, and patients with highly reactive tuberculinic tests. That, nevertheless, must not restrict the administration of TMZ, but, rather, stand for a warning about its possible toxicity, and thus mitigate complications.

Meningeal carcinomatosis in solid tumors / Carcinomatose meníngea em tumores sólidos

The involvement of the leptomeninges by metastatic tumors can be observed in solid tumors, in which case it is termed meningeal carcinomatosis (MC), and in lymphoproliferative malignant disease. It is more common in breast and lung cancer, as well as melanoma, with adenocarcinoma being the most frequent histological type. MC is usually a late event, with disseminated and progressive disease already present and, it is characterized by multifocal neurological signs and symptoms. Diagnosis is based on the evaluation of clinical presentation, cerebrospinal fluid and neuroimaging studies. The better systemic disease control is observed with new therapeutic agents, and the development of neuroimaging methods is responsible for the increasing incidence of such metastatic evolution. Intrathecal chemotherapy is generally the treatment of choice, although frequently palliative. Prognosis is guarded, although a higher performance status may indicate a subgroup of patients with a more favorable outcome.

O acometimento leptomeníngeo por metástases tumorais pode ocorrer em tumores sólidos, sendo chamado de carcinomatose meníngea (CM), e também em doenças linfoproliferativas. Tumores de mama, pulmão e melanoma são os principais responsáveis pelos casos, e adenocarcinoma é a histologia mais frequentemente encontrada. A CM é um evento tardio na evolução da doença e caracteriza-se por sinais e sintomas neurológicos multifocais. O diagnóstico se faz pela avaliação conjunta do quadro clínico, neuroimagem e estudo do líquido cefalorraquidiano. O maior controle da doença sistêmica obtido com as novas modalidades terapêuticas e a baixa penetração de drogas no sistema nervoso central, aliados ao desenvolvimento nos métodos de neuroimagem observado nas últimas décadas, são fatores que respondem por um aumento na incidência desta apresentação. A quimioterapia intratecal é o tratamento de escolha, porém, frequentemente paliativo. O prognóstico é reservado, sendo que o melhor performance status pode selecionar um subgrupo de pacientes com melhor evolução.

Paliative chemotherapy based in etoposide Leucovorin and 5 Fluorouracil (ELF) using leucovorin in low dose in the treatment of patients with advanced gastric cancer

A great percentage of diagnosed gastric cancer cases are encountered in advanced stages with distant metastases. In these cases, the standard treatment is palliative chemotherapy. In the ELF chemotherapy regime, the dose of leucovorin (Lv) varies from 300 to 500mg/m2. However, there are no studies that demonstrate therapeutic equivalence between high and low doses of Lv. OBJECTIVE: Retrospectively analyze the response rates and toxicity profile of the ELF scheme with low doses of Lv offered to patients with metastatic gastric cancer. MATTERS AND METHODS: Evaluated were patients treated with etoposide (120mg/m2/day), Lv (20mg/m2/day) and 5-fluorouracil (500mg/m2/day), D1 and D3 cycles repeated every three weeks. RESULTS: Sixty-eight patients were treated, 69% men, with median age of 60.24 years. Occurred six complete responses (8.8%), five partial responses (7.4%) and 38.2% of the patients presented stable disease. The median overall survival was 9.15 months (IC95%, 6.06-12.95), while patients with overall response was 16.05 months (IC95%, 10.48-21.63) and in those that presented stable disease or progression was 9.01 months (IC95%, 4.71-13.31; p=0.669). Grade III and IV low frequency toxicity was observed. CONCLUSIONS: In the present sample, the ELF regime with low-dose leucovorin presented an excellent toxicity profile. In spite of the low response rate, the respondent patients presented an equivalent overall survival to the other regimens of the literature.

Ameloblastoma: a case report

Ameloblastoma is a neoplasm arising from the epithelium involved with the formation of teeth. They are usually benign, locally aggressive and recurrent, however, metastases are rare. The treatment is not clearly defined and the main therapeutic tool is surgical intervention. Radiotherapy and chemotherapy have not been shown encouraging results. As there are few cases reported in the medical literature and the treatment is challenging, we reported a case of a 53-year-old woman with recurrentameloblastoma, with local and distant recurrence, that remains alive over 25 years from diagnosis.

Marcadores tumorais: a visäo prática do oncologista brasileiro / Tumor markers: pratical use by brazilian oncologists

O objetivo primário do estudo foi verificar a utilizaçäo dos marcadores tumorais na prática clínica diária. Utilizando a lista de endereços da Sociedade Brasileira de Oncologia Clínica, 330 questionários foram enviados, direcionados ao uso dos marcadores tumorais. Trinta porcento dos questionários foram retornados . As indicaçöes para rastreamento populacional, seguimento de doença tratada com intençäo curativa e tratamento de doença metastática foram heterogêneas. A inconstância das respostas fortalece a necessidade de uma padronizaçäo nacional no uso de marcadores tumorais.