An introduction to male breast cancer for urologists: epidemiology, diagnosis, principles of treatment, and special situations.

Breast cancer (BC) is mainly considered a disease in women, but male BC (MaBC) accounts for approximately 1.0% of BC diagnoses and 0.5% of malignant neoplasms in the western population. The stigmatization of MaBC, the fact that men are less likely to undergo regular health screenings, and the limited knowledge of health professionals about MaBC contribute to men being diagnosed at more advanced stages. The aim of this article is to increase the visibility of MaBC among urologists, who have more contact with male patients. This review highlights key points about the disease, the risk factors associated with MaBC, and the options for treatment. Obesity and increased population longevity are among the important risk factors for MaBC, but published studies have identified family history as extremely relevant in these patients and associated with a high penetrance at any age. There is currently no screening for MaBC in the general population, but the possibility of screening in men at high risk for developing BC can be considered. The treatment of MaBC is multidisciplinary, and, because of its rarity, there are no robust clinical studies evaluating the role of systemic therapies in the management of both localized and metastatic disease. Therefore, in current clinical practice, treatment strategies for men with breast cancer are extrapolated from information arising from studies in female patients.

HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer.

PURPOSE: Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC. METHODS: Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0. RESULTS: In total, 855 HER2-negative patients were identified. The median follow-up was 59 months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0. CONCLUSION: Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.

Combination of ifosfamide and etoposide as a salvage regimen for previously treated soft tissue sarcomas: a retrospective single centre study.

Introduction: Systemic treatment for metastatic soft tissue sarcoma (STS) results in modest activity in second and further lines. The aim of this study was to evaluate the efficacy of ifosfamide and etoposide (IE) as a salvage regimen for patients with metastatic STS. Methods: A retrospective, single centre study included patients with STS treated with IE from 2010 to 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints were toxicity, response rate (RR) and overall survival (OS). Survival was estimated by the Kaplan-Meier method and log-rank test used to compare the groups. Results: A total of 33 patients were identified, median age was 43 years, 60% were female, 12 had leiomyosarcoma. IE was used in second line in 51.5% and in >third line in 30.3% of patients. Median number of cycles was four and treatment discontinuation due to grade 3/4 toxicity occurred in 30.3%. The objective RR was 9% and the disease control rate was 60.6%. Median PFS was 4 months (95% CI, 2.1-5.9) and the median OS was 15 months (95% CI, 7.1-22.9). In the univariate analysis, smoking history, line of therapy and prior response to previous chemotherapy were prognostic factors for PFS. Conclusion: IE showed activity in previously treated STS, but with a non-negligible toxicity profile, worse than that with other available therapies. The use of the IE combination is not supported by our findings outside a clinical trial for soft part sarcomas.

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Genetic Landscape of Male Breast Cancer.

Male breast cancer (MBC) is now considered molecularly different from female breast cancer (FBC). Evidence from studies indicates that common genetic and epigenetic features of FBC are not shared with those diagnosed in men. Genetic predisposition is likely to play a significant role in the tumorigenesis of this rare disease. Inherited germline variants in BRCA1 and BRCA2 account for around 2% and 10% of MBC cases, respectively, and the lifetime risk of breast cancer for men harboring BRCA1 and BRCA2 mutations is 1.2% and 6.8%. As for FBC, pathogenic mutations in other breast cancer genes have also been recently associated with an increased risk of MBC, such as PALB2 and CHEK2 mutations. However, while multigene germline panels have been extensively performed for BC female patients, the rarity of MBC has resulted in limited data to allow the understanding of the magnitude of risk and the contribution of recently identified moderate penetrance genes of FBC for MBC predisposition. This review gathers available data about the germline genetic landscape of men affected by breast cancer, estimated risk associated with these genetic variants, and current guidelines for clinical management.

An introduction to male breast cancer for urologists: epidemiology, diagnosis, principles of treatment, and special situations

ABSTRACT Breast cancer (BC) is mainly considered a disease in women, but male BC (MaBC) accounts for approximately 1.0% of BC diagnoses and 0.5% of malignant neoplasms in the western population. The stigmatization of MaBC, the fact that men are less likely to undergo regular health screenings, and the limited knowledge of health professionals about MaBC contribute to men being diagnosed at more advanced stages. The aim of this article is to increase the visibility of MaBC among urologists, who have more contact with male patients. This review highlights key points about the disease, the risk factors associated with MaBC, and the options for treatment. Obesity and increased population longevity are among the important risk factors for MaBC, but published studies have identified family history as extremely relevant in these patients and associated with a high penetrance at any age. There is currently no screening for MaBC in the general population, but the possibility of screening in men at high risk for developing BC can be considered. The treatment of MaBC is multidisciplinary, and, because of its rarity, there are no robust clinical studies evaluating the role of systemic therapies in the management of both localized and metastatic disease. Therefore, in current clinical practice, treatment strategies for men with breast cancer are extrapolated from information arising from studies in female patients.

Sarcoma de Kaposi em Paciente Jovem Imunocompetente: uma Quinta Variante Epidemiológica? ­ Relato de Caso / Kaposi's Sarcoma in Young Immunocompetent Patient: a Fifth Epidemiological Variant? ­ Case Report / Sarcoma de Kaposi em Paciente Joven Inmunocompetente: ¿una Quinta Variante Epidemiológica? ­ Informe de Caso

Introdução: O sarcoma de Kaposi apresenta, classicamente, quatro tipos de variantes: clássico, endêmico, associado à imunossupressão (ou iatrogênico) e epidêmico (ou relacionado à Aids). Todos esses subtipos estão relacionados ao herpes-vírus humano 8. Uma quinta variante clínico-epidemiológica vem sendo proposta na literatura, que inclui uma apresentação visceral da doença no grupo de homens que fazem sexo com homens sem fatores de imunossupressão identificados. Relato de caso: Descreve-se o caso de um paciente masculino de 24 anos de idade, de orientação homossexual, sem fatores de imunossupressão, com apresentação linfonodal de sarcoma de Kaposi, e sem outros fatores que o incluam dentro das classificações da doença atualmente conhecidas. O paciente recebeu tratamento quimioterápico com paclitaxel, atingindo resposta completa e mantida até o momento, 42 meses após o término do tratamento. Conclusão: Esse caso reforça que a patogênese do sarcoma de Kaposi ainda é pouco clara, e que provavelmente múltiplos fatores, tanto do vírus como do hospedeiro, interajam entre si para desencadear a carcinogênese. É possível que o hábito sexual não encerre relação com essa patogênese, comportando-se apenas como fator confundidor. O paciente apresentou toxicidade mínima durante o tratamento com paclitaxel e atingiu resposta completa e mantida.

Introduction: Kaposi sarcoma classically presents four types of variants: classic, endemic, immunosuppression-associated (or iatrogenic) and epidemic (or AIDS-associated). All subtypes are invariably linked to human herpesvirus-8. A fifth clinical-epidemiological variant has been proposed in the literature, which includes a visceral presentation of the disease in the group of men who have sex with men without detected immunosuppressive factors. Case Report: We report the case of a 24-year-old male patient with a homosexual orientation without immunosuppressive factors, diagnosed with KS, with lymph node involvement, and without other disease characteristics that could include him within the currently known four types of Kaposi sarcoma classification. The patient received chemotherapy with paclitaxel, evolving with complete and sustained reponse until now, 42 months after the ending of treatment. Conclusion: This case reinforces that the pathogenesis of KS is still unclear, and that probably multiple factors, both virus and host, interact with each other to trigger carcinogenesis. It is possible that the sexual habit does not influence this pathogenesis, behaving only as a confounding factor. The patient had minimal toxicity during treatment with paclitaxel and achieved a complete and sustained response.

Introducción: El sarcoma de Kaposi presenta, clásicamente, cuatro tipos de variantes: clásico, endémico, asociado a inmunosupresión (o iatrogénico) y epidémico (o relacionado a SIDA). Todos estos subtipos están relacionados con el virus del herpes humano tipo 8 (HHV-8). Una quinta variante clínica-epidemiológica está en estudio, incluye una presentación visceral de la enfermedad en un grupo de hombres que tienen sexo con hombres sin factores de inmunosupresión de causa detectada. Informe de Caso: Se desarrolló un estudio sobre un paciente masculino de 24 años de edad, de orientación homosexual, sin factores de inmunosupresión, presentando diagnóstico de sarcoma de Kaposi con característica linfonodal de la enfermedad, y sin otros factores que incluyan dentro de las clasificaciones de sarcoma de Kaposi actualmente conocidas. El paciente recibió tratamiento quimioterápico con paclitaxel, alcanzando respuesta completa y sostenida hasta el momento, 42 meses después del término del tratamiento. Conclusión: Este caso refuerza que la patogénesis del sarcoma de Kaposi es poco clara, y que probablemente múltiples factores, tanto del virus y del hospedador, interactúan entre sí para desencadenar La carcinogénesis. Es posible que el hábito sexual no encierre relación con esa patogénesis, comportándose apenas como factor confundidor. El paciente presentó toxicidad mínima durante el tratamiento y alcanzó una respuesta completa y sostenida hasta el momento, pudiendo, el paclitaxel, ser considerado una opción sólida para el tratamiento del sarcoma de Kaposi en ese grupo de pacientes con esa variante de presentación.

[Persistence of dengue symptoms in patients in Uberaba, Minas Gerais State, Brazil]. / Persistência dos sintomas de dengue em uma população de Uberaba, Minas Gerais, Brasil.

The clinical picture of dengue is characterized by a maximum duration of 14 days despite frequent complaints of longer symptoms. This study evaluated the occurrence of persistent symptoms (> 14 days) and its impact on daily life. A hundred eighteen patients were interviewed, and the main symptoms at diagnosis were mialgia (98.3%), fever (97.5%) and weakness (95.8%). The presence of at least a persistent symptom was related by 77 (65.2%) individuals of wich 10 (8.5%) described it as intense and lasting for 30 days or more. The most persistent symptoms mentioned were weakness (58 cases), hiporexia (49) and sleepiness (40), occurring mostly in women, with odds ratio: 5.4 (IC95%: 2.3-12.3). A significant association between the persistence of the symptoms and the history of extra expenses (p = 0,02) was found, as well as a delay to return to normal activities (p < 0.001). Thus, it was verified that dengue presented a relevant impact on every day life, even after 14 days, a fact wich was associated with the presence of persistent symptoms of the illness.

Persistência dos sintomas de dengue em uma população de Uberaba, Minas Gerais, Brasil / Persistence of dengue symptoms in patients in Uberaba, Minas Gerais State, Brazil

O quadro clínico clássico de dengue caracteriza-se por duração máxima de 14 dias, embora freqüentemente pacientes refiram prolongamento dos sintomas. Este estudo avaliou a ocorrência de sinais e sintomas persistentes (> 14 dias) e seu impacto no cotidiano do indivíduo doente. Foram entrevistados 118 pacientes, cujos principais sintomas ao diagnóstico foram mialgia (98,3 por cento), febre (97,5 por cento) e fraqueza (95,8 por cento). A presença de pelo menos um sintoma persistente foi referida por 77 (65,2 por cento) entrevistados, sendo que 10 (8,5 por cento) relataram sua permanência de maneira intensa e por 30 dias ou mais. Os sintomas persistentes mais mencionados foram fraqueza (58 casos), hiporexia (49) e sonolência (40), ocorrendo mais no gênero feminino, com odds ratio: 5,4 (IC95 por cento: 2,3-12,3). Houve associação significativa entre a persistência dos sintomas e o relato de gastos adicionais (p = 0,02), e com o retorno às atividades habituais (p < 0,001). Assim, foi verificado que o dengue apresentou impacto na vida dos indivíduos, mesmo depois de 14 dias, sendo tal fato associado à presença de sintomas persistentes da doença.

The clinical picture of dengue is characterized by a maximum duration of 14 days despite frequent complaints of longer symptoms. This study evaluated the occurrence of persistent symptoms (> 14 days) and its impact on daily life. A hundred eighteen patients were interviewed, and the main symptoms at diagnosis were mialgia (98.3 percent), fever (97.5 percent) and weakness (95.8 percent). The presence of at least a persistent symptom was related by 77 (65.2 percent) individuals of wich 10 (8.5 percent) described it as intense and lasting for 30 days or more. The most persistent symptoms mentioned were weakness (58 cases), hiporexia (49) and sleepiness (40), occurring mostly in women, with odds ratio: 5.4 (IC95 percent: 2.3-12.3). A significant association between the persistence of the symptoms and the history of extra expenses (p = 0,02) was found, as well as a delay to return to normal activities (p < 0.001). Thus, it was verified that dengue presented a relevant impact on every day life, even after 14 days, a fact wich was associated with the presence of persistent symptoms of the illness.