Acupuncture on the Blood Flow of Various Organs Measured Simultaneously by Colored Microspheres in Rats

We examined how acupuncture affected the blood flow of muscle, kidney, stomach, small intestine, brain, lung, heart, spleen and liver. Wistar rats anesthetized with urethane (n = 27) were allocated into the control (n = 10), ST-7 (Hsia-Kuan, n = 10) and LI-4 (Hoku, n = 7) groups. To measure organ blood flow, colored microspheres (CMS) were injected through a catheter positioned in the left ventricle and blood samples were drawn from the femoral artery. Yellow CMS (3.6–4.2 × 105) and blue CMS (6.0–6.9 × 105) were injected at intervals of about 30 min. An acupuncture needle (φ 340 μm) was inserted into the left ST-7 point (left masseter muscle) or the right LI-4 point after the first sampling and left for about 30 min (10 twists at 1 Hz, 2-min intervals). The mean blood flow of nine organs varied widely from 4.03 to 0.20 (ml/min/g). Acupuncture to the ST-7 produced significant changes of the blood flow (percentage change from baseline) in the muscle, kidney, brain and heart (P < 0.05, versus control), but those of LI-4 were not significant. The blood flow of the left masseter muscle after acupuncture to ST-7 (left masseter muscle) tended to increase (P = 0.08). Changes in blood pressure during the experimental periods were almost similar among these three groups. Acupuncture stimulation increases the blood flow of several organs by modulating the central circulatory systems, and the effects differed with sites of stimulation

Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial

IMPORTANCE Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear. OBJECTIVE To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized (1: 1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m(2)) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries. INTERVENTION Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year. MAIN OUTCOMES AND MEASURES The primary objectivewas DFS; secondary objectives included distant disease-free survival, overall survival, cardiac DFS, and safety. RESULTS In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease-free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m(2) had inferior and those treated with 100 mg/m(2) had similar DFS as patients in the 1-year group. CONCLUSIONS AND RELEVANCE Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.Peer reviewe

NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy

Breast cancer is globally the most common malignancy in women. Her2-targeted monoclonal antibodies are established treatment modalities, and vaccines are in late-stage clinical testing in patients with breast cancer and known to promote tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity. It is therefore increasingly important to study immunological consequences of conventional treatment strategies. In this study, functional tests and four-colour flow cytometry were used to detect natural killer (NK)-cell functions and receptors as well as T-cell signal transduction molecules and intracellular cytokines in preoperative breast cancer patients, and patients who had received adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age-matched healthy controls. The absolute number of NK cells, the density of NK receptors as well as in vitro quantitation of functional NK cytotoxicity were significantly higher in preoperative patients than the post-treatments group and controls. A similar pattern was seen with regard to T-cell signalling molecules, and preoperative patients produced significantly higher amounts of cytokines in NK and T cells compared to other groups. The results indicate that functions of NK and T cells are well preserved before surgery but decrease following adjuvant therapy, which may speak in favour of early rather than late use of immunotherapeutic agents such as trastuzumab that may depend on intact immune effector functions

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Support Group Intervention in Primary Breast Cancer : Health-Related Quality of Life, with Special Reference to Anxiety, Depression and Fatigue

The aim of this thesis was to investigate in a (RCT) the effect of support group intervention in women with primary breast cancer in the short term, and with a long-term follow-up. Women with primary breast cancer were randomized between April 2002 and November 2007 and stratified according to adjuvant treatment with chemotherapy. Of 382 eligible patients, 191+191 patients were randomized to intervention and control groups respectively. Control patients were subjected to standard follow-up procedures. Patients in the intervention group received support intervention at the Foundation of Lustgården Mälardalen during one week followed by four days of follow-up two months later. Patients in intervention and control groups filled in questionnaires at baseline, after 2, 6 and 12 months and in the long-term follow-up after a mean of 6.5 years. In paper I, we studied the effect of the intervention on anxiety and depression measured by the HAD scale and we could show that a significantly lower proportion of women in the intervention group had high anxiety scores compared with women in the control group after 12 months; however, the proportion of women with high depression scores were unaffected. In paper II, we studied the effect of the intervention on fatigue and health-related quality of life (HRQoL) measured by the Norwegian version of the fatigue questionnaire (FQ) and EORTC-QLQ 30 and BR 23.We could not demonstrate any significant effect of the intervention. In paper III, we studied the effect of the intervention on sick-leave, healthcare utilization and the effect of the intervention in economic terms. We used a specially formulated questionnaire. There was a trend towards longer sick leave and more health-care utilization in the intervention group. The difference in total costs was statistically significantly higher in the intervention group after 12 months (p= 0.0036). In paper IV, we studied the long-term effects of the support intervention on anxiety, depression, fatigue and HRQoL. We could show a significant effect of the intervention on cognitive function, body image, future perspective and fatigue, the largest effect was seen among women who received chemotherapy; however, no effects on anxiety and depression were demonstrated