Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer.

Biological changes that occur during metastatic progression of breast cancer are still incompletely characterized. In this study, we compared intrinsic molecular subtypes and gene expression in 123 paired primary and metastatic tissues from breast cancer patients. Intrinsic subtype was identified using a PAM50 classifier and χ2 tests determined the differences in variable distribution. The rate of subtype conversion was 0% in basal-like tumors, 23.1% in HER2-enriched (HER2-E) tumors, 30.0% in luminal B tumors, and 55.3% in luminal A tumors. In 40.2% of cases, luminal A tumors converted to luminal B tumors, whereas in 14.3% of cases luminal A and B tumors converted to HER2-E tumors. We identified 47 genes that were expressed differentially in metastatic versus primary disease. Metastatic tumors were enriched for proliferation-related and migration-related genes and diminished for luminal-related genes. Expression of proliferation-related genes were better at predicting overall survival in metastatic disease (OSmet) when analyzed in metastatic tissue rather than primary tissue. In contrast, a basal-like gene expression signature was better at predicting OSmet in primary disease compared with metastatic tissue. We observed correlations between time to tumor relapse and the magnitude of changes of proliferation, luminal B, or HER2-E signatures in metastatic versus primary disease. Although the intrinsic subtype was largely maintained during metastatic progression, luminal/HER2-negative tumors acquired a luminal B or HER2-E profile during metastatic progression, likely reflecting tumor evolution or acquisition of estrogen independence. Overall, our analysis revealed the value of stratifying gene expression by both cancer subtype and tissue type, providing clinicians more refined tools to evaluate prognosis and treatment. Cancer Res; 77(9); 2213-21. ©2017 AACR.

IBD or strongyloidiasis?

Introduction: Strongyloides has been shown to infrequently mimic inflammatory bowel disease (IBD) or to disseminate when a patient with IBD and unrecognized strongyloides is treated with immunosupression. Case report: A man from Ecuador, living in Spain for years, with a history of type 2 diabetes mellitus and psoriasis treated with topical corticosteroids, was admitted to the hospital with an 8-month history of diarrhoea. Blood tests showed hyperglycemia, hyponatremia, elevated CRP and faecal calprotectin. Colonoscopy suggested IBD. The patient improved with steroids, pending biopsy results, and he was discharged. Biopies were compatible with IBD, but careful examination revealed strongyloides. He was given a prescription of albendazole. He had to be readmitted due to SIADH, which resolved with fluid restriction. Upon discharge albendazole was prescribed again. The patient skipped most of the out-patientclinic visits. He returned a year later on 10 mg/week methotrexate, asymptomatic, with 20% eosinophilia, and admitting he had never taken the strongyloides treatment for economical reasons. He then received a week of oral albendazol at the hospital. Biopsies and blood cell count were afterwards normal (eosinophils 3.1%) and serology for strongyloides antibodies was negative. Discussion: This case is of interest for four rarely concurring reasons. It´s a worm infection that mimics IBD; the infection was diagnosed by colon biopsy; the infection caused a SIADH; and, most interestingly, even though the patient is on immunosupression, he remains asymptomatic (AU)

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IBD or strongyloidiasis?

INTRODUCTION: Strongyloides has been shown to infrequently mimic inflammatory bowel disease (IBD) or to disseminate when a patient with IBD and unrecognized strongyloides is treated with immunosupression. CASE REPORT: A man from Ecuador, living in Spain for years, with a history of type 2 diabetes mellitus and psoriasis treated with topical corticosteroids, was admitted to the hospital with an 8-month history of diarrhoea. Blood tests showed hyperglycemia, hyponatremia, elevated CRP and faecal calprotectin. Colonoscopy suggested IBD. The patient improved with steroids, pending biopsy results, and he was discharged. Biopies were compatible with IBD, but careful examination revealed strongyloides. He was given a prescription of albendazole. He had to be readmitted due to SIADH, which resolved with fluid restriction. Upon discharge albendazole was prescribed again. The patient skipped most of the out-patient-clinic visits. He returned a year later on 10 mg/week methotrexate, asymptomatic, with 20% eosinophilia, and admitting he had never taken the strongyloides treatment for economical reasons. He then received a week of oral albendazol at the hospital. Biopsies and blood cell count were afterwards normal (eosinophils 3.1%) and serology for strongyloides antibodies was negative. DISCUSSION: This case is of interest for four rarely concurring reasons. It´s a worm infection that mimics IBD; the infection was diagnosed by colon biopsy; the infection caused a SIADH; and, most interestingly, even though the patient is on immunosupression, he remains asymptomatic.

Cáncer de mama y embarazo. Análisis de una serie de 27 pacientes / Breast cancer and pregnancy. Analysis of a series of 27 patients

Objetivo: Realizar un análisis descriptivo de la serie de pacientes con cáncer de mama (CM) y embarazo diagnosticadas en nuestro centro en relación con los métodos terapéuticos empleados y supervivencia global de la serie. Pacientes y métodos: Entre 1982 y 2009, de 5.906 pacientes diagnosticadas de CM, se trató a 27 pacientes con CM y embarazo (0,46%). Analizamos las características clínicas y anatomopatológicas, el diagnóstico, los tratamientos y la evolución de estas pacientes en nuestro centro. Resultados: La edad media al diagnóstico fue de 35 años. Durante la gestación se diagnosticó a 21 pacientes y en el posparto, a 6. El retraso medio diagnóstico desde el inicio de los síntomas fue de 4 meses. Respecto al perfil inmunohistoquímico determinado en 19 pacientes, 5 (26%) eran receptor 2 de factor de crecimiento epidérmico humano (HER2) positivo; otros 5 (26%), triple negativo; 3, luminal A, y en las 6 restantes, luminal B. Al diagnóstico, se clasificó a 5, 9, 11 y 2 pacientes en estadio I, II, III y IV, respectivamente. Histológicamente, 21 (78%) eran carcinomas ductales infiltrantes; 11 (41%), de alto grado histológico, y 4 casos (15%) presentaron características de carcinoma tipo inflamatorio al diagnóstico. Se pautó quimioterapia neoadyuvante en 16 pacientes (59%), sin que se detectaran complicaciones fetales. Se operó a todas las pacientes, y se realizó mastectomía radical modificada en 24 (89%), así como cirugía conservadora en 3. Con un tiempo medio de seguimiento de 60 meses, la supervivencia global fue del 70%. Cuatro pacientes (15%) presentaron recaída local y 13 (48%), recaída sistémica. Conclusiones: El carcinoma de mama durante el embarazo se asocia con un retraso diagnóstico, estadios avanzados y grados histológicos altos. El tratamiento quirúrgico conlleva un alto porcentaje de mastectomías radicales. La quimioterapia no produjo efectos adversos en el feto tras el primer trimestre de gestación. El pronóstico de CM durante el embarazo es similar al de las pacientes no gestantes de la misma edad y estadio tumoral (AU)

Objective: To perform a descriptive analysis of patients with breast cancer (BC) and pregnancy diagnosed in our centre, as regards the therapeutic methods used and the overall survival of the series. Patients and methods: Between 1982-2009, 5906 patients were diagnosed with BC, of whom 27 (0.46%) were treated for pregnancy-associated BC. We analysed the characteristics, diagnosis, treatments and outcome of these patients in our centre. Results: The mean age at diagnosis was 35 years. Twenty-one patients were diagnosed during pregnancy and six of them in the post-partum period. The mean diagnostic delay from the onset of symptoms was four months. In the immunohistochemical profile performed in 19 patients, 5 (26%) were HER2, 5 (26%) were triple-negative, luminal A in three patients, and luminal B in the other 6 cases. At diagnosis, 5, 9, 11 and 2 patients were classified into stages I, II, III and IV, respectively. Histologically, 21 (78%) were infiltrating ductal carcinomas, 11 (41%) were high grade carcinomas and 4 (15%) were inflammatory carcinomas at diagnosis. Neoadjuvant chemotherapy was prescribed in 16 patients (59%), with no foetal complications detected. All patients underwent surgery; 24 (89%) had modified radical mastectomy while three had conservative surgery. The mean follow-up time was 60 months, in which the overall survival was 70%. Four patients (15%) had local recurrence and 13 (48%) had systemic recurrence. Conclusions: Breast carcinoma during pregnancy is associated with diagnostic delay, advanced stages and high histological grades. Surgical treatment involves a high percentage of radical mastectomies. Chemotherapy did not produce adverse effects in the foetus after the first trimester. The prognosis for BC during pregnancy is similar to that of non-pregnant patients of the same age and tumour stage(AU)