First-line therapy in HER2 positive metastatic breast cancer. Is the mosaic fully completed or are we missing additional pieces?

The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early-stage and advanced HER2-positive breast cancer (BC). HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC. This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti-HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described. In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles. There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective

Activity of eribulin mesylate in brain metastasis from breast cancer. a stone in a pond?

Background: Brain metastases develop in approximately 10-25% of patients with metastatic breast cancer (MBC) and are associated with a very poor prognosis. Case Report: We report the case of a 40-year-old woman with MBC and associated lung, bone, liver, and brain metastases, who experienced a time to progression of several months with eribulin after whole-brain radiotherapy (WBRT), 2 lines of chemotherapy, and 1 line of hormonal therapy, maintaining a good toxicity profile. Discussion: Eribulin, in association with local treatment such as WBRT, can be well tolerated and effective in achieving a long progression-free survival and a good control of brain metastases in patients with MBC who have received multiple lines of treatment. The vascular remodeling properties of eribulin, combined with brain radiotherapy, might facilitate the passage of eribulin across the blood brain barrier, improving brain response. Conclusion: Our anecdotal experience suggests that eribulin may have a potentially beneficial effect on brain metastases while maintaining a good systemic control of the disease in patients with MBC

Impressive long-term response with pertuzumab and trastuzumab in HER2-positive breast cancer with brain metastasis

This is a case report of a 40-year-old woman who, after conservative breast cancer treatment, developed a HER2 positive solitary brain metastasis in the left temporal lobe, without extracranial disease. She underwent surgery resection followed by stereotactic radiotherapy and, because of early brain progression, she was submitted to the first line therapy with pertuzumab, trastuzumab and weekly paclitaxel. After six months of treatment, a brain magnetic resonance imaging revealed a complete disappearance of brain recurrence, which persisted for more than 24 months

The course of cancer related fatigue up to ten years in early breast cancer patients. What impact in clinical practice?

Little is known about the cancer related fatigue (CRF) along cancer course and risk factors that could predict CRF development and persistence in breast cancer (BC) survivors. This prospective study detected incidence, timing of onset, duration of CRF, impact on QoL and psychological distress. Seventy-eight early BC patients, undergoing chemotherapy (CT) followed or not by hormonal therapy were assessed for QoL and psychological distress by EORTC QLQC30 and HADs questionnaires. Fatigue was investigated with mix methods, structured interview and psychometric measures. A qualitative analysis was added to assess the behavioral pattern of CRF. Low fatigue levels were identified after surgery (9%), increasing during (49%) and at the end of CT (47%), maintaining after 1 year (31%) and declining up to ten years of follow-up. Prevalence of CRF was higher at the end of CT and lower at follow-up. At the end and after 1 and 2 years from CT, persistence of CRF was associated to anxiety in 20%, 11% and 5% and to depression in 15%, 10% and 5% respectively. A relationship between CRF and psychological distress was observed; patients presenting depression and anxiety before CT were at higher risk for fatigue onset at a later period. A relationship between fatigue and QoL was noted at the end of CT. Our study shows the fatigue timely trend in early BC patients from surgery, CT and follow-up. Identification of biological, psychological, social predictor factors related to fatigue could be helpful for early interventions in patients at higher risk of developing fatigue

Noncommutative Corrections to the Robertson-Walker metric

Upon applying Chamseddine's noncommutative deformation of gravity we obtain the leading order noncommutative corrections to the Robertson-Walker metric tensor. We get an isotropic inhomogeneous metric tensor for a certain choice of the noncommutativity parameters. Moreover, the singularity of the commutative metric at $t=0$ is replaced by a more involved space-time structure in the noncommutative theory. In a toy model we construct a scenario where there is no singularity at $t=0$ at leading order in the noncommutativity parameter. Although singularities may still be present for nonzero $t$, they need not be the source of all time-like geodesics and the result resembles a bouncing cosmology.Comment: 13 page

A Study of Risk Management Practice of Highway Projects in Nigeria

Construction Risk Management must be given adequate attention in order to ensure a successful project that meets the expectation of project goals and objectives thus risk management practice in Nigeria with respect to highway projects is explored in this study. Questionnaire survey was adopted for a population of 82 professionals (highway engineers, quantity surveyors and land surveyors) in clients, consultants and contracting organisations, using stratified random sampling techniques. The data collected were analysed by determination of the mean of the responses from the respondents and one way Analysis of Variance (ANOVA). Result of the analysis showed that; lack of accepted industry model for analysis of risk is rated as the most influencing factor in the implementation of risk management practice in Nigeria, followed by human/ organizational resistance. There is no significant difference at 5% level of significance between the responses of the clients, consultants and contractors on risk identification tools usage and risks response tools usage, risks analysis techniques usage of all the respondents except algorithms and Monte Carlo simulation. The result further showed that risk management practice is low in Nigeria, as all the respondents agreed that the use of rule of thumbs in managing construction risks associated with highways is prevalent as against modern techniques that are widely in use in developed countries. The study recommended adequate training for all stakeholders in highway construction sector to improve management of risks thus meeting project goals of time, approved budgets, and quality, imbibing the health and safety culture,  and in an environmentally acceptable manner. Keywords: Development, Highways, Risk management

Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer. Efficacy in combination with hormonal therapy

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not.Results: Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev.Conclusion: Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents

Efektifitas Ekstrak Tanaman Meniran (Phyllanthus Niruri) Sebagai Antibakteri Edwardsiella Tarda Secara in Vitro [Effectivity of Meniran (Phyllanthus Niruri) Extract as Edwardsiella Tarda Antibacterial According in Vitro]

Medicinal plants proven to effectively cope with bacterial diseases one of which is the plant meniran (Phyllanthus niruri). Phyllanthus niruri can act as an antibacterial because it has an antibacterial ingredient content of flavonoids, alkaloids, phenols, and tannins. This shows that plants can be used as an antibacterial Phyllanthus niruri of E.tarda. The purpose of this study was to determine the ability of the antibacterial of Phyllanthus niruri extracts and to find out the best concentration of Phyllanthus niruri extracts as antibacterial E.tarda according in vitro. The experiment was conducted in January 2011, housed at the Laboratory of Bacteriology Juanda Fish Quarantine Center and Laboratory of Organic Chemistry and Technology Faculty of Airlangga University Saints. This research method is done by the Minimum Inhibitor Concentration (MIC) and Minimum Bacterial Concentration (MBC) with 12 treatment. The results showed that the best concentration for the treatment of the concentration of 0.0313 g / ml as indicated with no growth of bacteria and is the lowest concentration of the dilution

Decapod crustaceans associated with an artificial reef (Adriatic Sea)

The aim of this study is to increase the knowledge on the distribution of decapod crustaceans associated with an artificial reef positioned on sandy-mud bottoms in the central Adriatic Sea. The reef is constituted of concrete modules assembled in pyramids and concrete poles. Hard and soft bottom samples were collected from 2001, just after reef construction, to 2005 (4 surveys per year). Regarding the soft seabed, three sites close to a pyramid, three inside the reef area at a distance of 10-15 m from the structures, and three 200 m outside the reef (control sites) were randomly sampled during each survey. At the same time, three pyramids (vertical and horizontal walls) and three poles were also investigated. After taxonomical analysis, decapod crustaceans were analysed using abundance and species richness. Sites and years were compared using a balanced, fixed effect, 2-way ANOVA and PERMANOVA. In addition, SIMPER analysis was performed to identify those species typifying each community inhabiting both the soft bottom and the artificial substrates. The results showed that the artificial reef induced an increase in both abundance and diversity of the decapods of the natural habitat. In fact, man-made substrates may offer new available space for biological colonization and allow the settlement of new species usually living on hard bottoms, thus increasing the complexity of the original benthic communities