Breast cancer and aneusomy 17: implications for carcinogenesis and therapeutic response.

Abnormalities of chromosome 17, recognised over two decades ago to be important in tumorigenesis, often occur in breast cancer. Changes of specific loci on chromosome 17 including ERBB2 amplification, P53 loss, BRCA1 loss, and TOP2A amplification or deletion are known to have important roles in breast-cancer pathophysiology. Numerical aberrations of chromosome 17 are linked to breast-cancer initiation and progression, and possibly to treatment response. However, the clinical importance of chromosome 17 anomalies, in particular the effect on ERBB2 protein expression, is unknown. Reports are conflicting regarding the association of copy gain of chromosome 17 (polysomy 17) with strong ERBB2 protein expression in the absence of true ERBB2 gene amplification. Copy-number anomalies in chromosome 17 seem to be common in tumours that show discrepant ERBB2 expression and in tumours with discordant ERBB2-protein and ERBB2 gene copy number measurements. The mechanisms of ERBB2 dosage changes-gene amplification versus chromosome gain and loss-probably differ in primary and metastatic disease; however, a correction for chromosome 17 copy-number is necessary to completely distinguish between these mechanisms. A better understanding of how polysomy 17 affects gene-copy number and protein expression will help to select patients who will respond to therapies targeting ERBB2 and other protein products of chromosome 17 loci.

Effect of Stellate Ganglion Block on Specific Symptom Clusters for Treatment of Post-Traumatic Stress Disorder.

This study assessed which symptoms are most impacted following stellate ganglion block (SGB) used to treat post-traumatic stress disorder (PTSD) symptoms. 30 active military service members with combat-related PTSD self-referred to their physician and psychologist. Patients were offered a SGB as part of their treatment program. Primary outcome was the magnitude of change for the 17 items on the PTSD Checklist-Military (PCL-M), which was administered the week before SGB, 1 week after SGB, and 2 to 4 months later. Mean PCL-M score decreased from 49 at baseline to 32, 1 week after the procedure (p < 0.001). 2 to 4 months after SGB, patients maintained an average PCL-M of 32. Patients reported greatest improvement in the first week after SGB for the following symptoms: irritability or angry outbursts, difficulty concentrating, and sleep disturbance. 2 to 4 months later, patients reported greatest improvement in the following: feeling distant or cut off, feeling emotionally numb, irritability or angry outbursts, and difficulty concentrating. SGB is a safe procedure that may provide extended relief for all clusters of PTSD symptoms. As a result of the significant reduction in hyperarousal and avoidance symptoms observed, this study supports incorporation of SGB into PTSD treatment plans.

HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial.

PURPOSE: We examined associations between tumor characteristics (human epidermal growth factor receptor 2 [HER2] protein expression, HER2 gene and chromosome 17 copy number, hormone receptor status) and disease-free survival (DFS) of patients in the N9831 adjuvant trastuzumab trial. PATIENTS AND METHODS: All patients (N = 1,888) underwent chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel with or without concurrent trastuzumab. HER2 status was determined by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) at a central laboratory, Mayo Clinic, Rochester, MN. Patients with conflicting local positive HER2 expression results but normal central laboratory testing were included in the analyses (n = 103). RESULTS: Patients with HER2-positive tumors (IHC 3+, FISH HER2/centromere 17 ratio ≥ 2.0, or both) benefited from trastuzumab, with hazard ratios (HRs) of 0.46, 0.49, and 0.45, respectively (all P < .0001). Patients with HER2-amplified tumors with polysomic (p17) or normal (n17) chromosome 17 copy number also benefited from trastuzumab, with HRs of 0.52 and 0.37, respectively (P < .006). Patients who received chemotherapy alone and had HER2-amplified and p17 tumors had a longer DFS than those who had n17 (78% v 68%; P = .04), irrespective of hormone receptor status or tumor grade. Patients with HER2-normal tumors by central testing (n = 103) seemed to benefit from trastuzumab, but the difference was not statistically significant (HR, 0.51; P = .14). Patients with hormone receptor-positive or -negative tumors benefited from the addition of trastuzumab, with HRs of 0.42 (P = .005) and 0.60 (P = .0001), respectively. CONCLUSION: These results confirm that IHC or FISH HER2 testing is appropriate for patient selection for adjuvant trastuzumab therapy. Trastuzumab benefit seemed independent of HER2/centromere 17 ratio and chromosome 17 copy number.

The epidemiology of United States high school soccer injuries, 2005-2007.

BACKGROUND: United States high school soccer participation increased 5 fold over the last 30 years. With increased participation comes increased injury incidence. HYPOTHESIS: High school soccer injury patterns will vary by gender and type of exposure. STUDY DESIGN: Descriptive epidemiologic study. METHODS: Soccer-related injury data were collected over the 2005-2006 and 2006-2007 school years from 100 nationally representative United States high schools via Reporting Information Online (RIO, an Internet-based sports-related injury surveillance system). RESULTS: Participating certified athletic trainers reported 1524 soccer injuries during 637 446 athlete exposures (AEs), for an injury rate of 2.39 per 1000 AEs, corresponding to a nationally estimated 807 492 soccer-related injuries during the 2005-2006 and 2006-2007 seasons. The injury rate per 1000 AEs was greater during competition (4.77) than practice (1.37) (rate ratio [RR] = 3.49; 95% confidence interval [CI], 3.15-3.87). Overall, the most frequent diagnoses were incomplete ligament sprains (26.8%), incomplete muscle strains (17.9%), contusions (13.8%), and concussions (10.8%). The most commonly injured body sites were the ankle (23.4%), knee (18.7%), head/face (13.7%), and thigh/upper leg (13.1%). Similar proportions of boys (57.9%) and girls (53.9%) returned to activity in <1 week. During competition, girls sustained complete knee ligament sprains requiring surgery at a rate of 26.4 per 100 000 AEs, higher than the rate among boys during competition (1.98 per 100 000 AEs) (RR = 13.3; 95% CI, 3.15-56.35) and among girls during practice (2.34 per 100 000 AEs) (RR = 11.3; 95% CI, 4.31-29.58). Player-to-player contact was more common among competition injuries (injury proportion ratio [IPR] = 2.42; 95% CI, 2.01-2.92), while noncontact mechanisms were more common among practice injuries (IPR = 2.39; 95% CI, 1.90-3.01). CONCLUSIONS: High school soccer injury patterns vary by gender and type of exposure. Identifying such differences in injury patterns is the important first step in the development of evidence-based, targeted injury prevention efforts.