Recently, phase I studies with novel antibody drug conjugates targeting HER2 suggested benefit in HER2-low patients -defined as immunohistochemistry(IHC) +1 or +2 FISH/ISH non-amplified, with advanced breast cancer(BC). Data on the prognostic value of HER2-low in early stage disease is scarce. The purpose of this study was to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy(NACT) and survival outcomes in early stage HER2negative BC. MethodsRecords from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. Primary objective was to compare differences between pathologic complete response(pCR) and relapse free survival(RFS) in luminal HER2-low/HER2-0 and triple negative(TNBC) HER2-low/HER2-0. Results855 non-HER2-positive patients were identified. Median follow-up was 59 months. 542 had luminal BC (63.4%) and 313 TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal tumors, 145 had HER2 IHC+1 (26.8%) and 91 IHC+2/ISH non-amplified (16.8%). In TNBC, only 36 had HER2 IHC+1 (11.5%) and 13 IHC+2/ISH non-amplified (4.2%). Among luminal/HER2-low and luminal/HER2-0 population, there was a high proportion of clinical T3/4 (61.5% vs 69.2%, p=0.053), node positive (74.2% vs 66.3%, p=0.27) and stage III tumors (63.1% vs 65%, p=0.51). The same was true TNBC/HER-low as compared to TNBC/HER2-0, despite a non-statistically significant higher cT4 among TNBC/HER-low (32.7% vs. 19.3%, p=0.17). pCR was 13% in luminal/HER2-low versus 9.5% in luminal/HER2-0 (p=0.27), and 51% in TNBC/HER2-low versus 47% in TNBC/HER2-0 (p=0.64). 5y RFS was 72.1% in luminal/HER2-low and 71.7% in luminal/HER2-0 (p=0.47), and 75.6% in TNBC/HER2-low versus 70.8% in TNBC/HER2-0 (p=0.23). HER2-low status was not associated with RFS in multivariate analysis (HR 0.83, 95%CI 0.6-1.11, p=0.21). ConclusionOur data does not support HER2-low as a biologically distinct BC subtype, with no predictive effect on pCR after NACT nor prognostic value on survival outcomes.

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.

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.

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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.