Summary Background We compared standard adjuvant anthracycline chemotherapy with anthracycline–taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the ...final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18–70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov , number NCT00688740. Findings Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90–126), disease-free survival was 62% (95% CI 58–65) for patients in the TAC group and 55% (51–59) for patients in the FAC group (hazard ratio HR 0·80, 95% CI 0·68–0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72–79) for patients in the TAC group and 69% (65–72) for patients in the FAC group (HR 0·74, 0·61–0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3–4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding Sanofi.
Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although ...accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS.
In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions.
Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate.
Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.
Summary Background Vascular endothelial growth factor (VEGF) has a crucial role in angiogenesis, and is a valid target in metastatic breast cancer. Motesanib is an investigational oral inhibitor of ...VEGF receptors. We aimed to determine whether treatment with motesanib plus paclitaxel is better than placebo plus paclitaxel in patients with HER2-negative locally recurrent or metastatic breast cancer. Methods Between Dec 1, 2006, and July 4, 2008, patients with untreated HER2-negative metastatic breast cancer were randomly assigned (using a randomisation list created by personnel not associated with the study) in a 1:1:1 ratio to paclitaxel (90 mg/m2 on days 1, 8, and 15 every 3 weeks) plus either masked motesanib 125 mg orally once per day (n=91), masked placebo orally once per day (n=94), or open-label bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle (n=97), after stratification according to adjuvant or neoadjuvant chemotherapy (taxane-containing regimens vs other regimens vs none), number of metastatic sites (<3 vs ≥3), and hormone receptor status (positive vs negative). Placebo was provided as a replica of motesanib 25 mg tablets. The primary endpoint was objective response rate (ORR) based on the population as assigned to treatment. This trial is registered with ClinicalTrials.gov , number NCT00356681. Findings ORRs for the motesanib group and the placebo group did not differ significantly (49% vs 41%; absolute difference 8% 95% CI −6 to 22; p=0·31). The ORR in the bevacizumab group (52%) was similar to that in the motesanib group. The most common grade 3 or higher adverse events included diarrhoea (18 of 92 patients in the motesanib group, none of 89 patients in the placebo group, and four of 96 patients in the bevacizumab group), fatigue (11, eight, and six), hypertension (11, one, and seven), and peripheral sensory neuropathy (ten, seven, and 19). More patients in the motesanib group had serious adverse events than did those in the placebo or bevacizumab groups (34, 26, and 21 patients, respectively); the most common of these in the motesanib group were gastrointestinal in nature. Interpretation Data from this trial do not support the further investigation of motesanib at this dose and schedule in this population. Funding Amgen.
Abstract Background Poor long-term success observed with current weight-control strategies stresses the relevance to explore new weight management approaches. Objective To assess the effects of a ...Health-At-Every-Size (HAES) intervention on eating behaviors, appetite sensations, metabolic and anthropometric variables, and physical activity levels in women at 6-month and 1-year postintervention. Design Randomized controlled trial; measurements at baseline, at the end of the intervention period (4 months), and at 6-month and 1-year postintervention (10 months and 16 months, respectively). Intervention and testing took place from September 2003 to August 2006. Participants/setting Premenopausal overweight/obese women (n=144; mean age of 42.3±5.6 years), recruited from free-living, general community. Intervention Women were randomly assigned to: HAES group (n=48), social support group (n=48), or control group (n=48). Main outcome measures Eating behaviors (restraint, disinhibition, and susceptibility to hunger), appetite ratings (desire to eat, hunger, fullness, and prospective food consumption), anthropometric and metabolic variables (body mass index, waist and hip circumferences, blood lipid levels, and blood pressure), and engagement in moderate to intense physical activity (energy cost ≥1.2 kcal×kg−1 ×15 minutes−1 ≥4.8 metabolic equivalents). Statistical analyses performed Changes for each dependent variable were assessed by linear mixed models according to a group (HAES vs social support vs control) by time (baseline vs 4 months vs 10 months vs 16 months) split-plot design. Results Situational susceptibility to disinhibition and susceptibility to hunger significantly decreased over time in both HAES group (−0.9±0.2 and −1.3±0.5, respectively) and the social support group (−0.4± 0.2 and −1.4±0.5, respectively). Although eating behavior scores observed at 16 months did not differ between HAES and social support groups (situational susceptibility to disinhibition: 2.5±0.2 in HAES group vs 2.7 ± 0.2 in social support group; susceptibility to hunger: 4.2±0.5 in both groups), they were lower in these groups than scores noted in the control group (3.3±0.2 for situational susceptibility to disinhibition and 5.9±0.5 for susceptibility to hunger). Conclusions These results suggest that, when compared to a control group, an HAES approach could have long-term beneficial effects on eating behaviors related to disinhibition and hunger. In addition, our study did not show distinctive effects of the HAES approach in comparison to a social support intervention.
