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Background:The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored.Methods:All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed.Results:In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0-69) and was significantly longer than in patients with BM and ECM (6 months, range 0-104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001).Conclusions:Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic central nervous system (mCNS) disease progression from breast cancer have a poor prognosis and often develop associated neurological complications. Human epidermal growth factor receptor 2 (HER2)-positivity status increases the risk of developing mCNS disease. Trastuzumab is an mAb that targets HER2 and is known to extend survival across all stages of HER2-positive breast cancer. [ABSTRACT FROM PUBLISHER]

Anti-Her-2/neu antibody is known to induce apoptosis in HER-2/neu overexpressing breast cancer cells. However, exact regulatory mechanisms mediating and controlling this phenomenon are still unknown. In the present study, we have investigated the effect of anti-Her-2/neu antibody on apoptosis of HER-2/neu overexpressing human breast cancer cell lines SK-BR-3, HTB-24, HTB-25, HTB-27, HTB-128, HTB-130 and HTB-131 in relation to p53 genotype and bcl-2 status. SK-BR-3, HTB-24, HTB-128 and HTB-130 cells exhibited mutant p53, whereas wild type p53 was found in HTB-25, HTB-27 and HTB-131 cells. All seven cell lines weakly expressed bcl-2 protein (10-20%). Anti-Her-2/neu antibody, irrespective of p53 and bcl-2 status, induced apoptosis in all 7 cell lines dose- and time-dependently and correlated with Her-2/neu overexpression. In addition, incubation of cell lines with anti-Her-2/neu antibody did not alter p53 or bcl-2 expression. Anti-HER-2/neu antibody did not induce apoptosis in HER-2/neu negative HBL-100 and HTB-132 cell lines. Our results indicate that within the panel of tested breast cancer cell lines, anti-Her-2/neu antibody-induced apoptosis was independent from the presence of intact p53. [ABSTRACT FROM AUTHOR]

Plasma levels of d-dimer, a degradation product of crosslinked fibrin, were determined in 73 patients with breast cancer. In these patients, significantly elevated plasma levels of d-dimer were found, as compared to healthy controls ( P<0.0001). In addition, we observed a moderate correlation between plasma levels of d-dimer and those of CA15-3 ( r=0.40; P<0.001) and between d-dimer and carcinoembryonic antigen ( r=0.39; P<0.01). Plasma levels of thrombin-antithrombin III complex (TAT), reflecting the activation of thrombin, were also significantly elevated in patients with breast cancer ( P<0.0001), and a poor, but significant correlation between carcinoembryonic antigen and TAT ( r= 0.25; P<0.05) was found. We conclude that the increase in plasma d-dimer and TAT levels might reflect an enhanced activation of the clotting system in patients with breast cancer. [ABSTRACT FROM AUTHOR]

A response by S. Beslija and colleagues to a letter to the editor about their article "Third consensus on medical treatment of metastatic breast cancer" published in the 2009 issue of the periodical is presented.

Background: Investigations originating from our laboratory have reported deficiencies in antigen presentation and functionality of monocytes derived from patients with early breast cancer (EBC), but not from healthy women with germline mutations of BRCA1. We have now expanded our investigations to dendritic cells (DC) which have been only insufficiently studied in patients with EBC in general and in healthy BRCA1 mutant carriers in particular. Methods: DC derived from patients with EBC and healthy women with BRCA1 mutations were analysed for the expression of DC-specific antigens CD1a, CD11c, CD83, CD80, CD86, CD54 and CD14 and of T cell-associated costimulatory molecules CD28 and CD152 (CTLA4). Antigen presentation by DCs was evaluated by a T-cell proliferation assay using tetanus toxoid (TT) as antigen. Peripheral blood was obtained from 36 patients with EBC, 5 healthy women with germline mutations of BRCA1 and from 26 healthy age-matched control persons. PBMC were prepared for ex vivo DC generation using GM-CSE IL4 and TNF-_ according to standard procedures. DC phenotype was examined by flow cytometry. T cell -- proliferation in response to TT-pulsed DCs was measured by (3H)thymidine assay. Results: DC derived from patients with EBC presented with a significantly reduced expression of DC-associated antigens CDla (p = 0.02), CD83 (p = 0.0001), CD80 (p = 0.01), CD86 (p < 0.0001)and CD54 (p < 0.000l) as compared to DC derived from healthy control females. Moreover, CD3- CD4- CD8- DC derived from the latter patient population had an obviously aberrant expression of costimulatory molecule CD28. In contrast, no significant differences in the expression of CD1a, CD86, CD83 and CD11c, hut significantly higher expression of costimulatory molecules CD80 (p = 0.003) and CD54 (p = 0.009) was found on DCs derived from healthy women with germline mutations of BRCA1, as compared to DCs derived from healthy women. Finally, T cell-proliferation in response to TT-pulsed autologous DCs was significantly decreased in patients with EBC, as compared to healthy control individuals (p < 0.0001). Conclusions: DCs derived from patients with EBC had not only an immature and aberrant phenotype, but also functional impairment in TT presentation which was not detectable prior to the development of disease in high-risk individuals with BRCA1 germline mutation. [ABSTRACT FROM AUTHOR]

This article summarizes statements and perspectives on breast cancer biology, identification of novel biological targets and optimal drug development with the aim of treatment individualization.Insights into tumour biology of breast cancer have led the path towards the introduction of targeted treatment approaches; still, breast cancer-related mortality remains relatively high. Efforts in the field of basic research revealed new druggable targets which now await validation within the context of clinical trials. Therefore, questions concerning the optimal design of future studies are becoming even more pertinent. Aspects such as the ideal end point, availability of predictive markers to identify the optimal cohort for drug testing, or potential mechanisms of resistance need to be resolved. An expert panel representing the academic community, the pharmaceutical industry, as well as European Regulatory Authorities met in Vienna, Austria, in November 2012, in order to discuss breast cancer biology, identification of novel biological targets and optimal drug development with the aim of treatment individualization. This article summarizes statements and perspectives provided by the meeting participants. [ABSTRACT FROM PUBLISHER]

The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer—update 2004. Lung Cancer 2005; 50: 129–137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771–1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer—update 2004. Lung Cancer 2005; 50: 129–137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771–1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic options. [ABSTRACT FROM PUBLISHER]