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

Have we detected the most luminous ULX so far?

We report the XMM-Newton detection of a moderately bright X-ray source superimposed on the outer arms of the inactive spiral galaxy MCG-03-34-63 (z=0.0213). It is clearly offset from the nucleus (by about 19'') but well within the D25 ellipse of the galaxy, just along its bar axis. The field has also been observed with the HST enabling us to compute a lower limit of > 94 on the X-ray to optical flux ratio which, together with the X-ray spectrum of the source, argues against a background AGN. On the other hand, the detection of excess X-ray absorption and the lack of a bright optical counterpart argue against foreground contamination. Short-timescale variability is observed, ruling out the hypothesis of a particularly powerful supernova. If it is associated with the apparent host galaxy, the source is the most powerful ULX detected so far with a peak luminosity of 1.35x10^41 erg/s in the 0.5-7 keV band. If confirmed by future multi-wavelength observations, the inferred bolometric luminosity (about 3x10^41 erg/s) requires a rather extreme beaming factor (larger than 115) to accommodate accretion onto a stellar-mass black hole of 20 solar masses and the source could represent instead one of the best intermediate-mass black hole candidate so far. If beaming is excluded, the Eddington limit implies a mass of >2300 solar masses for the accreting compact object.Comment: MNRAS Letters in press; minor correction at the end of Section

GRB Observed by IBIS/PICsIT in the MeV Energy Range

We present the preliminary results of a systematic search for GRB and other transients in the publicly available data for the IBIS/PICsIT (0.2-10 MeV) detector on board INTEGRAL. Lightcurves in 2-8 energy bands with time resolution from 1 to 62.5 ms have been collected and an analysis of spectral and temporal characteristics has been performed. This is the nucleus of a forthcoming first catalog of GRB observed by PICsIT.Comment: 6 pages, 3 figures. Poster presented at COSPAR 2008. Advaces in Space Research, accepted for publicatio

Simbol-X Background Minimization: Mirror Spacecraft Passive Shielding Trade-Off Study

The present work shows a quantitative trade-off analysis of the Simbol-X Mirror Spacecraft (MSC) passive shielding, in the phase space of the various parameters: mass budget, dimension, geometry, and composition. A simplified physical (and geometrical) model of the sky screen, implemented by means of a GEANT4 simulation, has been developed to perform a performance-driven mass optimization and evaluate the residual background level on Simbol-X focal plane.Comment: 3 pages, 6 figures, to appear in the proceedings of the second Simbol-X International Symposium "Simbol-X - Focusing on the Hard X-ray Universe", AIP Conf. Proc. Series, P. Ferrando and J. Rodriguez ed

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer. Clinical results and biological observations in taxane-pretreated patients

Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes. Patients and methods: The aim of this prospective, single-center open-label, noncomparative study was to evaluate the efficacy and safety of nab-paclitaxel in MBC patients pretreated with taxanes. The patients were treated with nab-paclitaxel as a single agent, 260 mg/m2 on day 1 of each 3-week cycle or 125 mg/m2 weekly. The primary endpoint was the overall response rate (ORR). Secondary objectives were duration of response, clinical benefit rate, progression-free survival (PFS), overall survival, and safety. Results: A total of 42 patients (median age 48 years, median Eastern Cooperative Oncology Group performance status 0, triple-negative MBC 19%, all pretreated with a taxane-based therapy, mainly in advanced disease) were enrolled in the study. The ORR was 23.8%, including one complete response (2.4%) and nine partial responses (21.4%); the disease control rate was 50%. The median duration of response was 7.2 months. After a median follow-up of 9 months, the median PFS was 4.6 months. ORR and PFS were similar irrespective of the previous chemotherapy lines, metastatic sites, and biomolecular expression. Nab-paclitaxel was well tolerated, and the most frequent treatment-related toxicities were mild to moderate (grades 1–2). Conclusion: This real-life study shows that nab-paclitaxel has a significant antitumor activity and a manageable safety profile in patients pretreated with taxanes and experiencing a treatment failure after at least one line of chemotherapy