Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: Phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel

Contains fulltext : 98255.pdf (publisher's version ) (Open Access)BACKGROUND: Today, more than 70% of patients with primary node-negative breast cancer are cured by local therapy alone. Many patients receive overtreatment by adjuvant chemotherapy due to inadequate risk assessment. So far, few clinical trials have prospectively evaluated tumor biology based prognostic factors. Risk assessment by a biological algorithm including invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) will assess up to 35-55% of node-negative patients as low-risk and thus avoid chemotherapy. In contrast, a clinical-pathological algorithm will only classify 20-40% of patients as low-risk. High-risk node-negative patients should receive chemotherapy. Anthracycline-based regimens are accepted as a standard, the additional benefit of taxanes remains an open question. METHODS/DESIGN: The international NNBC3 ("Node Negative Breast Cancer 3-Europe") trial compares biological risk assessment (UP) using invasion factors uPA/PAI-1 with a clinical-pathological algorithm (CP). In this trial, the type of risk assessment (CP or UP) was chosen upfront by each center for its patients. Fresh frozen tissue was obtained to determine uPA/PAI-1 using an enzyme-linked immunosorbent assay (ELISA). Patients assessed as high-risk were stratified by human epidermal growth factor receptor 2 (HER2) status and then randomised to receive anthracycline-containing chemotherapy 5-Fluorouracil (F)/Epirubicin (E)/Cyclophosphymide (C) or an anthracycline-taxane sequence (FE(100)C*6 versus FE(100)C*3 followed by Docetaxel(100)*3). DISCUSSION: In this trial, 4,149 node-negative patients with operable breast cancer from 153 centers in Germany and France were included since 2002. Measurement of uPA/PAI-1 by ELISA was performed with standardised central quality assurance for 2,497 patients (60%) from 56 "UP"-centers. The NNBC 3-Europe trial showed that inclusion of patients into a clinical phase III trial is feasible based on biological testing of fresh frozen tumor material. In addition, 2,661 patients were classified as high-risk and thus received chemotherapy. As adjuvant chemotherapy, 1,334 high-risk patients received FE(100)C-Docetaxel(100), and 1,327 received French FE(100)C. No unexpected toxicities were observed. Chemotherapy efficacy and comparison of UP with CP will be evaluated after longer follow-up. TRIAL REGISTRATION: clinical Trials.gov NCT01222052

A propos de l'information écrite (étude sur 45 femmes atteintes d'un cancer du sein non métastatique, sur le type d'information et sur le moment de délivrance de celle-ci)

L'information orale est obligatoire et l'information écrite recommandée. L'objectif de ce travail est de déterminer, d'une part, quel type d'information écrite préfèrent les patientes, d'autre part, a quel moment les patientes sont-elles le plus disposées à recevoir une information écrite, et enfin quelle méthode permet de discerner devant une patiente vue en consultation pour la première fois lequel des deux livrets lui sera la plus profitable. Nous décidons de réaliser une enquête prospective randomisée en double sur l'information écrite donnée à des patientes atteintes d'un cancer du sein et débutant un traitement. 45 patientes sont réparties en trois Bras, appelé A, B et C. Les patientes reçoivent l'information écrite à des moments différents suivant le Bras d'inclusion. Deux questionnaires et un entretien sont utilisés. Nous analysons les réponses en fonction du moment de délivrance: les Bras A, B et C et en fonction des déterminants sociaux des patientes: l'âge, le métier, le niveau d'étude et le mode de vie. Conclusion l'âge est un facteur déterminant. Les patientes de plus de 60 ans, ne souhaitent pas recevoir d'information écrite systématiquement, souhaitent en générale une information écrite concise et rassurante et préfèrent que l'information leur soit donnée lors du traitement. Les patientes de moins de 60 ans, désirent recevoir une information écrite, souhaitent en générale une information complète et détaillée et préfèrent que l'information leur soit donnée lors de la consultation d'annonce.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Mechanical Behaviour of Hi-Nicalon Fibre-Reinforced Si3N4 Matrix Composites under Monotonic and Fatigue Tensile Loading

Fully dense SiC / Si3N4 were fabricated by slurry infiltration followed by hot-pressing. Two types of pyrolytic carbon coating were deposited at the fibre-matrix interface and resulted in clearly different interfacial properties thus mechanical behaviour . Composite "A" showed a higher monotonic tensile strenght (700 MPa) and a better fatigue limit (550 MPa) compared to composite "B" (620 MPa and 450 MPa respectively). Interfacial properties were assessed by modelling of hysteresis loops.JRC.(IAM)-Institute For Advanced Material

Transverse Strain Response of Hi-Nicalon Fibre Reinforced Silicon Nitride Matrix Composites.

In this paper, the Etr response of a series of Hi-Nicalon (SiC) fibre reinforced silicon nitride matrix composites is studied. At first, the processing route of the material is briefly described. Axial and transverse tensile mechanical behaviour, along with matrix crack density measurements , are then shown. Characterisation of the interface properties and evaluation of thermal residual stresses, obtained by modelling of axial hysterisis loops are finally presented. This is followed by a short description of a micromechanical model for the Etr response UD- CMCs. To conclude, experimental and theoretical transverse strain evolution are compared and discussed.JRC.(IAM)-Institute For Advanced Material

A higher body mass index and fat mass predict the reduction of dose-intensity for docetaxel but not for epirubicin in early breast cancer chemotherapy

International audienc

Decreased spontaneous electrical activity in neuronal networks exposed to radiofrequency 1800 MHz signals

International audienceThe rapid development of wireless communications has raised questions about their potential health risks. So far, the only identified biological effects of radiofrequency fields (RF) are known to be caused by heating. but the issue of potential nonthermal biological effects, especially on the central nervous system (CNS), remains open. We previously reported a decrease in the firing and bursting rates of neuronal cultures exposed to a Global System for Mobile (GSM) RF field at 1,800 MHz for 3 min (Moretti D. Garenne A, Haro E, Poulleier de Gannes F. Lagroye I, Leveque P, Veyret B. Lewis N. Bioelectromagnetics 34 571-578, 2013). The aim of the present work was to assess the dose-response relationship for this effect and also to identify a potential differential response elicited by pulse-modulated GSM and continuous-wave (CW) RF fields. Spontaneous bursting activity of neuronal cultures from rat embryonic cortices was recorded using 60-electrode multielectrode arrays (MEAs). At 17-28 days in vitro, the neuronal cultures were subjected to 15-min RF exposures, at specific absorption rates (SAR) ranging from 0.01 to 9.2 W/kg. Both GSM and CW signals elicited a clear decrease in bursting rate during the RF exposure phase. This effect became more marked with increasing SAR and lasted even beyond the end of exposure for the highest SAR levels. Moreover, the amplitude of the effect was greater with the GSM signal. Altogether. our experimental findings provide evidence for dose-dependent effects of RF signals on the bursting rate of neuronal cultures and suggest that part of the mechanism is nonthermal. NEW and NOTEWORTHY In this study, we investigated the effects of some radiofrequency (RF) exposure parameters on the electrical activity of neuronal cultures. We detected a clear decrease in bursting activity, dependent on exposure duration. The amplitude of this effect increased with the specific absorption rate (SAR) level and was greater with Global System for Mobile signal than with continuous-wave signal, at the same average SAR. Our experiment provides unique evidence of a decrease in electrical activity of cortical neuronal cultures during RF exposure

Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment

International audienceBackground. The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC). Patients and Methods. The participants were newly diagnosed EBC patients aged $65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin 6 docetaxel [CT1 group], n 5 58) or radiotherapy for patients who did not receive chemotherapy (CT2 group, n 5 61), and at the same interval for the healthy controls (n 5 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index. Results. Forty-nine percent of the patients (mean age, 70 6 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT1 group had more subjective cognitive complaints after treatment (p 5 .008). The oldest patients (aged 70–81 years) tended to have more objective decline with docetaxel (p 5 .05). Conclusion. This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. The Oncologist 2016;21:1–12 Implications for Practice: This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with che-motherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs

Baseline cognitive functions among elderly patients with localised breast cancer

International audiencePURPOSE: Cognitive deficits (CD) are reported among cancer patients receiving chemotherapy, but may also be observed before treatment. Though elderly patients are expected to be more prone to present age-related CD, poor information is available regarding the impact of cancer and chemotherapy on this population. This study assessed baseline cognitive functions (before adjuvant treatment) in elderly early stage breast cancer (EBC) patients. METHODS: Women >65years-old with newly diagnosed EBC were included in this prospective study. Episodic memory, working memory, executive functions and information processing speed were assessed by neuropsychological tests. Questionnaires were used to assess subjective CD, anxiety, depression, fatigue, quality of life and geriatric profile. Objective CD were defined using International Cognition and Cancer Task Force criteria. A group of elderly women without cancer coupled with published data related to healthy women were used for comparison (respectively to subjective and objective CD). RESULTS: Among the 123 elderly EBC patients (70±4years) included, 41% presented objective CD, which is greater than expected in healthy population norms (binomial test P<.0001). Verbal episodic memory was mainly impaired (21% of patients). No correlation was observed between objective CD and cancer stage or geriatric assessment. Subjective CD only correlated with verbal episodic memory (P=.01). CONCLUSIONS: This is the first large series assessing baseline cognitive functions in elderly EBC patients. More than 40% presented objective CD before any adjuvant therapy, which is higher than what is reported among younger patients. Our results reinforce the hypothesis that age is a risk factor for CD in EBC patients

Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): An open-label, randomised phase 3 trial

BACKGROUND: Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy. METHODS: In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379. FINDINGS: Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 15·9 months (IQR 9·1-21·7) in the chemotherapy-alone group and 16·1 months (10·6-22·7) in the combination group. Progression-free survival was significantly longer for those patients treated with bevacizumab plus chemotherapy than for those with chemotherapy alone (median: 6·3 months [95% CI 5·4-7·2] vs 4·2 months [3·9-4·7], respectively, stratified hazard ratio [HR] 0·75 [95% CI 0·61-0·93], two-sided stratified log-rank p=0·0068). The most common grade 3 or more adverse events were hypertension (33 [13%] of 245 patients receiving bevacizumab plus chemotherapy vs 17 [7%] of 238 patients receiving chemotherapy alone), neutropenia (29 [12%] vs 20 [8%]), and hand-foot syndrome (27 [11%] vs 25 [11%]). Grade 3 proteinuria occurred in 17 (7%) of 245 patients receiving combination therapy and one (<1%) of 238 patients receiving chemotherapy alone. Serious adverse events were reported in 61 (25%) of 245 patients receiving bevacizumab plus chemotherapy versus 44 (18%) of 238 patients receiving chemotherapy alone. INTERPRETATION: These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy