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

Evolution of magnetic fields and energetics of flares in active region 8210

To better understand eruptive events in the solar corona, we combine sequences of multi-wavelength observations and modelling of the coronal magnetic field of NOAA AR 8210, a highly flare-productive active region. From the photosphere to the corona, the observations give us information about the motion of magnetic elements (photospheric magnetograms), the location of flares (e.g., H$\alpha$, EUV or soft X-ray brightenings), and the type of events (H$\alpha$ blueshift events). Assuming that the evolution of the coronal magnetic field above an active region can be described by successive equilibria, we follow in time the magnetic changes of the 3D nonlinear force-free (nlff) fields reconstructed from a time series of photospheric vector magnetograms. We apply this method to AR 8210 observed on May 1, 1998 between 17:00 UT and 21:40 UT. We identify two types of horizontal photospheric motions that can drive an eruption: a clockwise rotation of the sunspot, and a fast motion of an emerging polarity. The reconstructed nlff coronal fields give us a scenario of the confined flares observed in AR 8210: the slow sunspot rotation enables the occurence of flare by a reconnection process close to a separatrix surface whereas the fast motion is associated with small-scale reconnections but no detectable flaring activity. We also study the injection rates of magnetic energy, Poynting flux and relative magnetic helicity through the photosphere and into the corona. The injection of magnetic energy by transverse photospheric motions is found to be correlated with the storage of energy in the corona and then the release by flaring activity. The magnetic helicity derived from the magnetic field and the vector potential of the nlff configuration is computed in the coronal volume. The magnetic helicity evolution shows that AR 8210 is dominated by the mutual helicity between the closed and potential fields and not by the self helicity of the closed field which characterizes the twist of confined flux bundles. We conclude that for AR 8210 the complex topology is a more important factor than the twist in the eruption process

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

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

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

insights into the effects of occupant behaviour lifestyles and building automation on building energy use

Abstract In order to optimize building energy consumption, Member States will have to establish minimum efficiency requirements for systems, and promote the introduction of active control system in new constructions or major renovations. Energy saving, plant efficiency and environmental sustainability are also factors delineating smart buildings. Interestingly, occupant behaviour is known to be one of the key sources of uncertainty in the prediction of building energy use. The success of automation strategies is recognized to be dependent on how the occupants interact with the building. The present research describes the effect of different building occupants' lifestyles and building automation on a high performing building

Occupant behaviour lifestyles and effects on building energy use: Investigation on high and low performing building features

Occupant behaviour is known to be one of the key sources of uncertainty in the prediction of building energy use. Extended literature reviews linked the large performance gaps between residential buildings with same properties and similar climate conditions to the way occupants interact with the building envelope and systems. Furthermore, in the last decades, more stringent energy codes have led to energy efficient design strategies with the aim of reaching the nearly-zero energy target. The success of these strategies is now heavily dependent on how the occupants interact with the building, or rather, on the energy-related lifestyles they assume. In line with this, the present study employs building simulations to demonstrate the potential impact of different occupant behaviour lifestyles on the energy use of a Mediterranean (i) residential nearly-zero energy building (nZEB) under-construction and a (ii) Reference Building (RB) whose envelope-driven loads dominate the consumption profile

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

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

Dental anomalies : prevalence and associations between them in a large sample of non-orthodontic subjects, a cross-sectional study

Background: To analyze the prevalence and associations between dental anomalies detectable on panoramic radiographs in a sample of non-orthodontic growing subjects. Methods: For this cross-sectional study, digital panoramic radiographs of 5005 subjects were initially screened from a single radiographic center in Rome. Inclusion criteria were: subjects who were aged 8–12 years, Caucasian, and had good diagnostic quality radiographs. Syndromic subjects, those with craniofacial malformation, or orthodontic patients were excluded and this led to a sample of 4706 subjects [mean (SD) age = 9.6 (1.2) years, 2366 males and 2340 females]. Sample was subsequently divided into four subgroups (8, 9, 10, and 11–12 year-old groups). Two operators examined panoramic radiographs to observe the presence of common dental anomalies. The prevalence and associations between dental anomalies were also investigated. Results: The overall prevalence of dental anomalies was 20.9%. Approximately, 17.9% showed only one anomaly, 2.7% two anomalies, while only 0.3% had more than two anomalies. The most frequent anomalies were the displacement of maxillary canine (7.5%), hypodontia (7.1%), impacted teeth (3.9%), tooth ankylosis (2.8%), and tooth transposition (1.4%). The lower right second premolar was the most frequent missing teeth; 3.7% had only one tooth agenesis, and 0.08% had six or more missing tooth (Oligodontia). Mesiodens was the most common type of supernumerary tooth (0.66%). Two subjects had taurodontic tooth (0.04%). Tooth transpositions and displacement of maxillary canine were seen in 1.4 and 7.5%, retrospectively (approximately 69 and 58% were in the 8 and 9 year-old groups, retrospectively). Significant associations were detected between the different dental anomalies (P < .05). Conclusions: The results of our study revealed significant associations among different dental anomalies and provide further evidences to support common etiological factors