Prognostic value of residual node involvement in operable breast cancer after induction chemotherapy

The purpose of this retrospective study was to evaluate the influence of axillary disease on patients' survival after neoadjuvant chemotherapy and to assess patient and tumor characteristics associated with post-chemotherapy axillary involvement.After six induction cycles, 277 patients with operable breast cancer (stage II–III) underwent surgery with axillary dissection, followed by radiotherapy (n = 267) or additional chemotherapy (n = 63) and adjuvant tamoxifen therapy (n = 138). At a median follow-up of 8.5 years, overall survival (OS) and disease-free survival (DFS) were analyzed as a function of node involvement.The differences in OS and DFS according to the number of positive nodes were highly statistically significant with a decreased survival associated with the increasing number of nodes (p = 5 × 10^–6 and 9 × 10^–7, respectively). Upon multivariate analysis, the node number after chemotherapy appeared as the most significant prognostic factor (p = 7 × 10^–4 for OS and p = 3 × 10^–5 for DFS). All the other classical prognostic factors were insignificant, except post-chemotherapy Scarff–Bloom–Richardson (SBR) grading for OS (p = 8 × 10^–4) and adjuvant hormonotherapy for DFS (p = 1 × 10^–2).Although constituting a different parameter from primary surgery data, the number of positive nodes after chemotherapy could still remain a valuable prognostic factor at secondary surgery, raising the question for high risk patients of a second non-cross-resistant adjuvant regimen, or high dose chemotherapy with peripheral blood stem cells support.     

A simple tool to evoke physicians' real training needs.

Commonly used methods for identifying the training needs of general practitioners do not enable the real needs felt during interviews with patients during office visits to be detected. In this study, the authors evaluate how physicians' use of a personal-office-visit diary affects the level of specificity of their expressed training needs. In 1999, the authors carried out a controlled intervention trial using a random sample of 1,038 general practitioners from a region of France, randomized to intervention and control groups. The practitioners in the intervention group were asked to identify their training needs using a personal-office-visit diary. The level of specificity for their expressed needs was compared with that of the expressed needs of the practitioners in the control group. The use of the diary was associated with a significantly higher level of specificity in the training needs identified by the general practitioners who participated. Independent of the intervention, practitioners under 40 years of age, those in urban practice, and those who were members of a continuing medical education (CME) association expressed their training needs with higher specificity. The personal-office-visit diary would seem to be a simple, inexpensive, and useful tool for more specifically identifying training needs, which could help establish more appropriate and better-targeted training programs. However, it should be assessed further by those involved in CME for general practitioners.     

Evaluation of the quantitative analytical methods real-time PCR for HER-2 gene quantification and ELISA of serum HER-2 protein and comparison with fluorescence in situ hybridization and immunohistochemistry for determining HER-2 status in breast cancer patients

BACKGROUND: HER-2 status is generally determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Both methods are only semiquantitative, require a tumor sample, and can be difficult to reproduce. We compared these methods with 2 quantitative approaches, one measuring HER-2 gene copy number in tissue by real-time quantitative PCR (qPCR), and the other measuring shed HER-2 protein in serum by ELISA in patients with metastatic disease. METHODS: We analyzed 52 cases of metastatic breast cancer for which both serum collected at the diagnosis of metastasis and stored primary breast tumor specimens were available. The within- and between-run imprecision of real-time qPCR and ELISA were evaluated according to Clinical and Laboratory Standards Institute (formerly known as NCCLS) recommendations. Concordance among the 4 methods was assessed by calculating the kappa statistic and its 95% confidence interval (95% CI). RESULTS: The CVs for within- and between-run imprecision were both <10% with qPCR and ELISA. There was good agreement of results between qPCR and IHC (kappa = 0.81; 95% CI, 0.64-0.99), qPCR and FISH (kappa = 0.77; 95% CI, 0.58-0.96), ELISA and IHC (kappa = 0.65; 95% CI, 0.41-0.89); and ELISA and FISH (kappa = 0.69; 95% CI, 0.46-0.92). CONCLUSIONS: Measurements of HER-2 gene expression by qPCR and of serum HER-2 protein by ELISA are highly reproducible approaches for determining HER-2 status in metastatic breast cancer. In addition, ELISA eliminates the need for biopsy.     

Influence of “living high–training low” on aerobic performance and economy of work in elite athletes

This study tested the effects of “living high-training low” (Hi–Lo) on aerobic performance and economy of work in elite athletes. Forty endurance athletes (cross-country skiers, swimmers, runners) performed 13–18 consecutive days of training at 1,200 m altitude, by sleeping at 1,200 m (LL, n = 20) or in hypoxic rooms with 5–6 nights at 2,500 m followed by 8–12 nights at 3,000–3,500 m (HL, n = 20). The athletes were evaluated before (pre-), one (post-1) and 15 days (post-15) after Hi–Lo. Economy was assessed from two sub-maximal tests, one non-specific (cycling) and one specific (running or swimming). From pre- to post-1: increased both in HL (+ 7.8%, P < 0.01) and in LL (+ 3.3%, P < 0.05), peak power output (PPO) tended to increase more (P=0.06) in HL (+ 4.1%, P < 0.01) than in LL (+ 1.9%). At post-15, has returned to pre-values in both groups, PPO increased more (P < 0.05) in HL (+ 8.3%, P < 0.01) than in LL (+ 3.8%), and power at respiratory compensation point (RCP) increased more (P < 0.05) in HL (+ 9.5%, P < 0.01 and + 11.2%, P < 0.01) than in LL (+ 3.2 and + 3.3%). Cycling mechanical efficiency (8–5%) and economy during specific locomotion (7–7%) increased (P < 0.05) in both groups. This study shows that, for a similar increase in HL had a greater increase in PPO than LL. The efficiency of Hi–Lo is also evidenced 15 days later by higher and power at RCP. This study emphasizes that during the post-altitude period, economy of work greatly increases in both groups.     

Dual targeting of HER1/EGFR and HER2 with cetuximab and trastuzumab in patients with metastatic pancreatic cancer after gemcitabine failure: results of the “THERAPY”phase 1-2 trial

To improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m², then 250mg/m²). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7–6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation.     

Colonic Motility and Transit After Intermesenteric Nerve Transection and Mesenteric Ganglionectomy in Dogs

Mechanical activity of the large intestine of fasted and fed conscious dogs was recorded with strain gauges, before and after intermesenteric nerve transection, inferior and superior mesenteric ganglia ablation, or inferior mesenteric ganglion ablation. Radiography performed at fixed intervals after a test meal containing barium sulfate was used to assess the transit rate of colonic contents. Modifications of the quantity of eliminated feces, the number of defecations, and fecal dry matter content were associated with transit disturbance. After surgery the cyclical organization of colonic motility persisted in both fasted and fed states. The cyclical fasted pattern remained unchanged, but the inhibitory colocolonic reflex disappeared. After mesenteric ganglia ablation, the fed state activity was enhanced and apparent colonie residence time was shortened. Associated with giant migrating contractions, the number of fecal evacuations increased, and their dry matter content decreased. Transit disturbances were still observed 5 months after the surgical procedures. We conclude that the cyclical organization of colonic motility did not require extrinsic nervous inputs. The mesenteric ganglia had a sympathetic inhibitory effect on postprandial colonic motility. The factor triggering this effect was related to the arrival of the digesta in the colon. Hyperreflexia of the entire colon induced immediate evacuation of the contents, preventing the normal distention of the colon for storage of feces.