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The conventional treatment currently applied in malignant brain tumors in adults consists of surgery, often followed by irradiation of the brain. The prognosis is not encouraging, as the survival median does not exceed 11 months [8, 17]. Studies by Frankel and German [5] showed that where surgery alone is used, the survival median is about 6 months after extensive exeresis and two, 5 months after partial exeresis. After simple biopsy, the spontaneous survival median is 10 months. Comparable results were reported in the retrospective work of Roth and Elwidge. Radiotherapy increases the survival median established after surgical treatment alone by about 4 months (Frankel and German [5]). Experimental results in animals [16], which were later confirmed in man [7, 10, 19, 20, 21, 23, 24, 4, 6], have shown the potential value of chemotherapy and led to the development of new therapeutic methods, despite the limited number of drugs available and the fact that their combined effect has not been studied [11].

Percutaneous placement of an intraneoplasmic electrode in pulmonary metastases of three patients with extrathoracic primary cancers permitted electrochemical treatment of these lesions. These reacted variably to anodic and cathodic electrodes. One breast cancer metastasis disappeared after treatment

Breast cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. In many patients, microscopic or clinically evident metastases have already occurred by the time the primary tumor is diagnosed. Chemotherapy or hormonal therapy reduces the risk of distant metastasis by one-third, but it is estimated that about 70% to 80% of patients receiving treatment would have survived without it. Therefore, being able to predict breast cancer metastasis can spare a significant number of breast cancer patients from receiving unnecessary adjuvant systemic treatment and its related expensive medical costs. Current studies have demonstrated the potential value of gene expression signatures in assessing the risk of post-surgical disease recurrence. However, most of these studies attempt to develop genetic marker-based prognostic systems to replace the existing clinical criteria, while ignoring the rich information contained in established clinical markers. Clinical markers, such as patient history and laboratory analysis, which are the basis of day-to-day clinical decision support, are often underused to guide the clinical management of cancer in the presence of microarray data. As a result, given the complexity of breast cancer prognosis, we proposed a novel strategy based on synergy network that utilize both clinical and genetic markers to identify the potential hybrid signatures and investigate their interactions which are associated with breast cancer metastasis. In this study, a computational method is performed on publicly available microarray and clinical data. A rigorous experimental protocol is used to estimate the prognostic performance of the hybrid signature and other prognostic approaches. The hybrid signature performs significantly better than other methods, including the 70-gene signature, clinical makers alone and the St. Gallen consensus criterion. At 90% sensitivity level, the hybrid signature achieves 77% specificity, as compared to 53% for the 70-gene signature and 43% for the clinical makers. The predicted results also showed a strong dependence of regulator genes that are related to cell death in cell development process. These significant gene regulators are useful to understand cancer biology and in producing new drug design.

INTRODUCTIONMetastatic spread from non-head and neck tumours to the sinonasal region is exceedingly rare. We present a case of breast cancer metastasis to the nasopharynx, ethmoid and sphenoid sinuses. To date there have been only two similar cases in the literature. We discuss the diagnosis and management of such cases and propose how they may be staged.PRESENTATION OF CASEA 75-year-old woman with past medical history of breast carcinoma, presented clinically as having a primary sinonasal malignancy. Magnetic resonance imaging (MRI) demonstrated a lesion involving the spenoid and ethmoid sinuses, nasendoscopy revealed a mass in the nasopharynx. Biopsy from clinic pointed to inverted sinonasal papilloma, however this did not fit with the MRI or the clinical picture. Repeat biopsy under image guidance revealed the lesion to be a breast cancer metastasis.DISCUSSIONAn extensive literature review revealed few cases of spread to the sinonasal region from distant primary malignancy. When such cases do arise, most are from renal tumours. Breast cancer metastases usually present with signs and symptoms of disseminated disease, however our case represents a true isolated metastasis. We discuss the management of our case and suggest the use of the tumour-node-metastasis (TNM) system, in order to stage these rare isolated occurrences.CONCLUSIONIf discovered early, this rare manifestation may be managed by primary surgical resection. Metastases to the region may be more common than previously thought. A high index of suspicion should be employed, especially where there is past medical history of malignancy.

Tumour metastasis is a property separate and additional to tumourigenicity, as demonstrated by the fact that several undeniably tumourigenic cell lines are incapable of forming metastatic colonies in distant sites even if deliberately disseminated by inoculation into the bloodstream. Evidence confirming this comes from studies on animals with malignant mammary neoplasms, as well as on patients with inoperable malignancy.

The condition involving the appearance of epithelioid non-classified granulomas, without signs of systemic sarcoidosis, is called sarcoid-like reaction. These granulomas are basically seen in the tumor or the lymph nodes that drain the tumor, and cannot be distinguished from malignancy by means of imaging techniques such as PET/CT. Such a condition may cause lesions to be considered as metastatic lesions in consequence of a misevaluation, and may lead to mistakes in the diagnosis, staging and treatment of the disease. In this study, a locally advanced breast cancer case, which involved the detection of a sarcoid-like reaction, is presented with the aim of increasing awareness regarding any potential mistakes that might occur during the diagnostic PET/CT processes, Sistemik sarkoidoz bulguları olmaksızın, epiteloid non-kazeifiye granülomların görülmesi halinde, bu duruma sarkoid benzeri reaksiyon adı verilmektedir. Bu granülomlar esas olarak tümör veya tümörü drene eden lenf nodlarında görülmekte ve PET/BT gibi görüntüleme yöntemleriyle de maligniteden ayırt edilememektedir. Bu durum, lezyonların yanlışlıkla metastaz olarak değerlendirilmesine yol açabilmekte ve hastalığın tanı, evreleme ve tedavisinde ciddi hatalara yol açarak telafisi mümkün olmayan sonuçlar doğurabilmektedir. Bu yüzden bu çalışmada; supraklavikular, paratrakeal ve subkarinal lenf nodu tutulumunun gözlendiği sarkoid reaksiyonlu, lokal ileri evre meme kanseri bir olgu sunulmuş ve PET/BT ile teşhiste oluşabilecek yanılgılar adına farkındalık yaratılmaya çalışılmıştır

Arising from: L. Ma, J. Teruya-Feldstein & R. A. Weinberg , 682–688 (2007)10.1038/nature06174 ; Ma et al. reply MicroRNAs regulate messenger RNA expression but are frequently dysregulated in tumours. Ma et al.1 report that overexpression of microRNA-10b (miR-10b) initiates invasion and metastasis in models of breast cancer and that its expression in primary breast carcinomas correlates with clinical progression. We tested this in patients with primary breast cancer, of whom 92 had nodal metastases at diagnosis and 127 were node-negative. We found no significant association between miR-10b levels and metastasis or prognosis. Although we concede that miR-10b may have a biological effect in a few cells at the growing edge of a tumour, we believe that it is unlikely to correlate in whole tumour samples with clinical progression.

Introduction Breast cancer metastasis is a complex, multi-step biological process. Genetic mutations along with epigenetic alterations in the form of DNA methylation patterns and histone modifications contribute to metastasis-related gene expression changes and genomic instability. So far, these epigenetic contributions to breast cancer metastasis have not been well characterized, and there is only a limited understanding of the functional mechanisms affected by such epigenetic alterations. Furthermore, no genome-wide assessments have been undertaken to identify altered DNA methylation patterns in the context of metastasis and their effects on specific functional pathways or gene networks. Methods We have used a human gene promoter tiling microarray platform to analyze a cell line model of metastasis to lymph nodes composed of a poorly metastatic MDA-MB-468GFP human breast adenocarcinoma cell line and its highly metastatic variant (468LN). Gene networks and pathways associated with metastasis were identified, and target genes associated with epithelial–mesenchymal transition were validated with respect to DNA methylation effects on gene expression. Results We integrated data from the tiling microarrays with targets identified by Ingenuity Pathways Analysis software and observed epigenetic variations in genes implicated in epithelial–mesenchymal transition and with tumor cell migration. We identified widespread genomic hypermethylation and hypomethylation events in these cells and we confirmed functional associations between methylation status and expression of the CDH1, CST6, EGFR, SNAI2 and ZEB2 genes by quantitative real-time PCR. Our data also suggest that the complex genomic reorganization present in cancer cells may be superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes. Conclusion This is the first whole-genome approach to identify genome-wide and gene-specific epigenetic alterations, and the functional consequences of these changes, in the context of breast cancer metastasis to lymph nodes. This approach allows the development of epigenetic signatures of metastasis to be used concurrently with genomic signatures to improve mapping of the evolving molecular landscape of metastasis and to permit translational approaches to target epigenetically regulated molecular pathways related to metastatic progression.

Liver metastasis from breast cancer usually results in the development of systemic metastasis. We report a breast cancer patient with an early isolated liver recurrence who survived more than 7 years with no recurrence. She was treated with aggressive HER2-directed chemotherapy and hepatic metastasectomy. Local hepatectomy with effective medical oncological therapy with curative intent is worth trying in patients with breast cancer liver metastasis.

Current concepts conceive “breast cancer” as a complex disease that comprises several very different types of neoplasms. Nonetheless, breast cancer treatment has considerably improved through early diagnosis, adjuvant chemotherapy, and endocrine treatments. The limited prognostic power of classical classifiers determines considerable over-treatment of women who either do not benefit from, or do not at all need, chemotherapy. Several gene expression based molecular classifiers (signatures) have been developed for a more reliable prognostication. Gene expression profiling identifies profound differences in breast cancers, most probably as a consequence of different cellular origin and different driving mutations and can therefore distinguish the intrinsic propensity to metastasize. Existing signatures have been shown to be useful for treatment decisions, although they have been developed using relatively small sample numbers. Major improvements are expected from the use of large datasets, subtype specific signatures and from the re-introduction of functional information. We show that molecular signatures encounter clear limitations given by the intrinsic probabilistic nature of breast cancer metastasis. Already today, signatures are, however, useful for clinical decisions in specific cases, in particular if the personal inclination of the patient towards different treatment strategies is taken into account.

Background Targeting the TGF-β1 pathway for breast cancer metastasis therapy has become an attractive strategy. We have previously demonstrated that naringenin significantly reduced TGF-β1 levels in bleomycin-induced lung fibrosis and effectively prevented pulmonary metastases of tumors. This raised the question of whether naringenin can block TGF-β1 secretion from breast cancer cells and inhibit their pulmonary metastasis. Methods We transduced a lentiviral vector encoding the mouse Tgf-β1 gene into mouse breast carcinoma (4T1-Luc2) cells and inoculated the transformant cells (4T1/TGF-β1) into the fourth primary fat pat of Balb/c mice. Pulmonary metastases derived from the primary tumors were monitored using bioluminescent imaging. Spleens, lungs and serum (n = 18–20 per treatment group) were analyzed for immune cell activity and TGF-β1 level. The mechanism whereby naringenin decreases TGF-β1 secretion from breast cancer cells was investigated at different levels, including Tgf-β1 transcription, mRNA stability, translation, and extracellular release. Results In contrast to the null-vector control (4T1/RFP) tumors, extensive pulmonary metastases derived from 4T1/TGF-β1 tumors were observed. Administration of the TGF-β1 blocking antibody 1D11 or naringenin showed an inhibition of pulmonary metastasis for both 4T1/TGF-β1 tumors and 4T1/RFP tumors, resulting in increased survival of the mice. Compared with 4T1/RFP bearing mice, systemic immunosuppression in 4T1/TGF-β1 bearing mice was observed, represented by a higher proportion of regulatory T cells and myeloid-derived suppressor cells and a lower proportion of activated T cells and INFγ expression in CD8+ T cells. These metrics were improved by administration of 1D11 or naringenin. However, compared with 1D11, which neutralized secreted TGF-β1 but did not affect intracellular TGF-β1 levels, naringenin reduced the secretion of TGF-β1 from the cells, leading to an accumulation of intracellular TGF-β1. Further experiments revealed that naringenin had no effect on Tgf-β1 transcription, mRNA decay or protein translation, but prevented TGF-β1 transport from the trans-Golgi network by inhibiting PKC activity. Conclusions Naringenin blocks TGF-β1 trafficking from the trans-Golgi network by suppressing PKC activity, resulting in a reduction of TGF-β1 secretion from breast cancer cells. This finding suggests that naringenin may be an attractive therapeutic candidate for TGF-β1 related diseases. Electronic supplementary material The online version of this article (doi:10.1186/s13058-016-0698-0) contains supplementary material, which is available to authorized users.

Background Identification of a gene expression signature in primary breast tumors that could classify patients by lymph node status would allow patients to avoid the morbidities of surgical disruption of the lymph nodes. Attempts to identify such a signature have, to date, been unsuccessful. Because breast tumor subtypes have unique molecular characteristics and different sites of metastasis, molecular signatures for lymph node involvement may vary by subtype. Methods Gene expression data was generated from HG U133A 2.0 arrays for 135 node positive and 210 node negative primary breast tumors. Intrinsic subtype was assigned using the BreastPRS. Differential gene expression analysis was performed using one-way ANOVA using lymph node status as the variable with a False-discovery rate