Nighttime compression supports improved self-management of breast cancer-related lymphedema: A multicenter randomized controlled trial.

BACKGROUND: Lymphedema is a prevalent long-term effect of breast cancer treatment associated with reduced quality of life. This study examined the efficacy of nighttime compression as a self-management strategy for women with chronic breast cancer-related lymphedema. METHODS: Th authors conducted a parallel 3-arm, multicenter, randomized trial. Women were recruited from 3 centers in Canada and randomized to group 1 (daytime compression garment alone [standard care]), group 2 (daytime compression garment plus nighttime compression bandaging), or group 3 (daytime compression garment plus the use of a nighttime compression system garment). The primary outcome was the change in excess arm volume from the baseline to 12 weeks. Participants from all groups used a nighttime compression system garment from weeks 13 to 24. RESULTS: One hundred twenty women were enrolled, 118 completed the randomized trial, and 114 completed the 24-week follow-up. The rates of adherence to nighttime compression were 95% ± 15% and 96% ± 11% in the compression bandaging and nighttime compression system groups, respectively. After the intervention, the addition of nighttime compression was found to be superior to standard care for both absolute milliliter reductions (P = .006) and percentage reductions (P = .002) in excess arm lymphedema volume. Significant within-group changes were seen for quality of life across all groups; however, no between-group differences were found (P > .05). CONCLUSIONS: The trial demonstrated a significant improvement in arm lymphedema volume from the addition of nighttime compression whether through the application of compression bandaging or through the use of a nighttime compression system garment. LAY SUMMARY: Lymphedema is swelling that occurs in the arm on the side of the surgery for breast cancer. Lymphedema occurs in approximately 21% of women. Lymphedema tends to worsen over time and can result in recurrent infections in the arm, functional impairment, and pain. Currently, treatment consists of intensive treatments to reduce the swelling followed by regular use of a compression sleeve during the day. This study examined and found a benefit from the addition of nighttime compression (whether through self-applied compression bandaging or through the use of a nighttime compression system garment) to the use of a daytime compression sleeve.

Evaluation of three commercial progesterone receptor assays in a single tamoxifen-treated breast cancer cohort.

Estrogen receptor and progesterone receptor status are routinely assessed using immunohistochemistry assays to assist in patient prognosis and clinical management. Three commonly utilized autostainer vendors-Dako, Leica and Ventana-provide ready-to-use progesterone receptor assays; however, they have never been directly compared in a single breast cancer cohort. We looked at three immunohistochemical progesterone receptor assays, in addition to original ligand-binding assay results, in a single retrospective, tamoxifen-treated breast cancer cohort to investigate inter- and intra-observer agreement, concordance, prognostic ability and measures of test performance. All immunohistochemical assays utilized the manufacturer's specified protocols. Five-year disease-free survival was the endpoint of interest, and multivariate models were adjusted for lymph node status, tumor grade, tumor size and human epidermal growth factor 2 status. All assays showed substantial to almost perfect agreement between the three observers (Dako κ=0.69-0.90; Leica κ=0.70-0.89; and Ventana κ=0.78-0.94) and concordance (Dako/Leica κ=0.81; Dako/Ventana κ=0.78; and Leica/Ventana κ=0.82). Univariate survival analyses showed that only the ligand-binding assay, Dako and Ventana assays achieved statistical significance. No statistically significant results were seen in multivariate models, although a strong trend was seen with the Ventana progesterone receptor assay. All assays performed similarly with regards to measures of test performance with ligand-binding assay set as the reference, and all immunohistochemical assays outperformed the ligand-binding assay in regards to 5-year disease-free survival. Despite similar agreement and concordance with the progesterone receptor assays, clear differences were noted with regards to 5-year disease-free survival. Additional survival analyses suggest that clinical utility of estrogen receptor assays vary when investigated in combination with progesterone receptor.

A systematic comparison of three commercial estrogen receptor assays in a single clinical outcome breast cancer cohort.

Breast cancers are routinely assessed for estrogen receptor status using immunohistochemical assays to assist in patient prognosis and clinical management. Specific assays vary between laboratories, and several antibodies have been validated and recommended for clinical use. As numerous factors can influence assay performance, many laboratories have opted for ready-to-use assays using automated stainers to improve reproducibility and consistency. Three commonly used autostainer vendors-Dako, Leica, and Ventana-all offer such estrogen receptor assays; however, they have never been directly compared. Here, we present a systematic comparison of three platform-specific estrogen receptor ready-to-use assays using a retrospective, tamoxifen-treated, breast cancer cohort from patients who were treated in Calgary, Alberta, Canada from 1985 to 2000. We found all assays showed good intra-observer agreement. Inter-observer pathological scoring showed some variability: Ventana had the strongest agreement followed closely by Dako, whereas Leica only showed substantial agreement. We also analyzed each estrogen receptor assay with respect to 5-year disease-free survival, and found that all performed similarly in univariate and multivariate models. Determination of measures of test performance found that the Leica assay had a lower negative predictive value than Dako or Ventana, compared with the original ligand-binding assay, while other measures-sensitivity, specificity, positive predictive value, and accuracy-were comparable between the three ready-to-use assays. When comparing against disease-free survival, the difference in negative predictive value between the vendor assays were not as extreme, but Dako and Ventana still performed slightly better than Leica. Despite some discordance, we found that all ready-to-use assays were comparable with or superior to the ligand-binding assay, endorsing their continued use. Our analysis also allowed for exploration of estrogen receptor-negative, progesterone receptor-positive cases, and we discovered that this phenotype was not consistent across the assays, suggesting this might be an artifact.

Efficacy of night-time compression for breast cancer related lymphedema (LYNC): protocol for a multi-centre, randomized controlled efficacy trial.

BACKGROUND: Lymphedema is a prevalent long-term effect of breast cancer treatment that is associated with reduced quality of life. More recent observational data suggest that the addition of night-time compression to day-time use of a compression garment results in better long-term control of arm lymphedema. The primary objectives of the randomized controlled phase of the trial are to determine the efficacy of night-time compression on arm lymphedema volume maintenance and quality of life in breast cancer survivors who have completed intensive reduction treatment for their lymphedema. METHODS/DESIGN: The study will be a parallel 3-arm, multi-centre randomized fast-track trial. A total of 120 women with breast cancer related lymphedema will be recruited from 3 centres in Canada and randomized to group 1: Day-time compression garment alone or Group 2: Day-time compression garment + night-time compression bandaging or Group 3: Day-time compression garment + use of a night-time compression system garment. The duration of the primary intervention period will be 12 weeks. The follow-up period after the intervention (weeks 13 to 24) will follow a longitudinal observational design. The primary outcome variables: differences from baseline to week 12 in arm volume and quality of life (Lymphoedema Functioning, Disability and Health Questionnaire: Lymph-ICF). Secondary outcomes include bioimpedance analysis, sleep disturbance and self-efficacy. All measurements are standardized and will be performed prior to randomization, and at weeks 6, 12, 18 and 24. DISCUSSION: The use of night-time compression as a self-management strategy for chronic breast cancer related lymphedema is seen as an innovative approach to improve long-term control over the condition. This trial aims to advance the knowledge on self-management strategies for lymphedema. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov on July 9(th), 2014 ( NCT02187289 ).

A teaching model for aromatase inhibitors after tamoxifen.

Breast cancer is the most common cancer diagnosed in women. The present study evaluated the family physicians' (FPs) understanding of adjuvant hormonal therapies for an early breast cancer. FPs were invited to attend teaching workshops on this topic, which utilized a pretest, didactic and interactive teaching, and posttest format. FPs (n = 23) showed an improvement (p < 0.001) in pretest to posttest score. It is clear that, with a targeted teaching, FPs can quickly become more knowledgeable on the topic of hormonal therapies in breast cancer, with the potential of applying this information in their own practice.

Secondary Neuroendocrine Carcinoma Following High-Dose Radiotherapy for Head and Neck Cancer: Report of Two Cases.

Patients treated with radiation have an increased risk of developing second cancers, of which carcinomas, sarcomas, and hematological malignancies have most commonly been reported. Neuroendocrine carcinomas (NEC) are rarely reported in patients previously treated with radiation. Two patients, who had successfully undergone chemoradiotherapy for head and neck cancers at our institution, developed secondary NEC within the radiation field more than five years after the treatment. Both patients underwent curative-intent treatment of secondary malignancies, one with chemotherapy, radiation and surgery (Case 1) and the other with chemotherapy and surgery (Case 2). Both had no evidence of disease at a short follow-up of twelve months (Case 1), and three months (Case 2) after treatment. NEC can develop post-radiotherapy; a multidisciplinary approach is necessary to successfully treat these patients.

Elevated factor VIII is a risk factor for idiopathic venous thromboembolism in Canada - is it necessary to define a new upper reference range for factor VIII?

Previous studies suggest elevated factor VIII is a common, independent risk factor for venous thromboembolism (VTE); however, these studies included secondary and idiopathic VTE. We sought to explore the association between elevated factor VIII and VTE in Canadian patients with idiopathic thrombosis, and confirm the current upper factor VIII reference range was appropriate. We enrolled 300 consecutive patients with idiopathic VTE who were matched to friend controls by age, sex and ethnicity. Factor VIII levels were measured and compared between cases and controls. The optimal cut-off value to designate factor VIII levels as elevated was determined using a variety of methods. The optimal upper cut-off value for factor VIII levels was 270 IU/dl. In the logistic regression analysis, cases were more likely to have elevated factor VIII levels (OR:8.76), as were females (OR:1.93) and older subjects (OR: 1.05). Factor VIII cutoffs for a 95% specificity by age were 238 IU/dl for subjects <40 years, 248 IU/dl age 40-55 years, 261 IU/dl age 56-70 years, and 313 IU/dl age >70. Our findings confirm that elevated factor VIII is associated with an increased risk of idiopathic VTE. In our patients and matched controls, the current upper limit of normal (150 IU/dl) for factor VIII is not of clinical use. We propose that the upper limit be increased to 270 IU/dl or individual labs should establish their upper limit if they wish their assays to be discriminatory in patients with VTE. Age specific cut-offs may be clinically relevant.

Primary results of ROSE/TRIO-12, a randomized placebo-controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer.

PURPOSE: Currently, antiangiogenic strategies in metastatic breast cancer have demonstrated modest improvements in progression-free survival (PFS) but not improved quality or duration of survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab is a human immunoglobulin G1 antibody that binds vascular endothelial growth factor receptor-2 and blocks ligand-stimulated activation. The ROSE/TRIO-012 trial evaluated ramucirumab with docetaxel in unresectable, locally recurrent, or metastatic breast cancer. PATIENTS AND METHODS: In this double-blind, placebo-controlled, randomized, multinational phase III trial, 1,144 patients with human epidermal growth factor receptor 2 (HER2) -negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomly assigned at a two-to-one ratio to receive docetaxel 75 mg/m(2) plus ramucirumab 10 mg/kg or docetaxel 75 mg/m(2) plus placebo once every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographic region. An independent data monitoring committee oversaw the trial. The primary end point was investigator-assessed PFS. RESULTS: Median PFS in patients treated with ramucirumab plus docetaxel was 9.5 months, compared with 8.2 months in patients who received placebo plus docetaxel (hazard ratio [HR], 0.88; P = .077). Median overall survival was 27.3 months in patients who received ramucirumab plus docetaxel, compared with 27.2 months in patients who received placebo plus docetaxel (HR, 1.01; P = .915). Toxicities seen at significantly higher rates in patients receiving ramucirumab included fatigue, hypertension, febrile neutropenia, palmar-plantar erythrodysesthesia syndrome, and stomatitis. CONCLUSION: Addition of ramucirumab to docetaxel in HER2-negative advanced breast cancer did not meaningfully improve important clinical outcomes.

Treatment of ocular metastasis with anti-VEGF: a literature review and case report.

PURPOSE: This is the first case report where 1.25mg intravitreal bevacizumab (IVB) correlated with choroidal mass resolution from metastatic breast cancer given concurrently with chemotherapy demonstrating, at best, disease stability in other organs. STUDY DESIGN: Case report. METHODS: Upon confirmation of choroidal, liver and bone metastasis from breast carcinoma, a 72-year-old female received four intravitreal bevacizumab 1.25mg injections based on the presence of subretinal and intraretinal fluid. Visual outcomes were analyzed by ophthalmologic evaluation, B-scan, fluorescein angiography, and optical coherence tomography. RESULTS: After 3 treatments of 1.25mg intravitreal bevacizumab, visual acuity improved from 20/125 OD to 20/30 OD. These results were maintained for 5 months, after which a 4th IVB injection was given to try to further improve visual outcomes. Following this, complete resolution of the mass was observed with remaining pigmentary changes and vision improved to 20/25 one month following this. IVB was administered concurrently to systemic chemotherapy that demonstrated at best disease stability in metastases in other organs. CONCLUSION: In this case 1.25mg intravitreal bevacizumab proved to be a safe, effective and relatively easy treatment for choroidal metastasis from breast cancer. An important benefit of intravitreal bevacizumab therapy for choroidal metastasis is the ease of administration and minimal time commitment required as compared to other therapies. Further studies should be conducted to confirm the appropriate dosing and long-term outcomes of intravitreal bevacizumab to treat choroidal metastasis.

Phase II trial of SarCNU in malignant glioma: unexpected pulmonary toxicity with a novel nitrosourea: a phase II trial of the national cancer institute of canada clinical trials group.

PURPOSE: A multi-centre phase II study of SarCNU-a novel chloroethylnitrosourea (CNU)-in patients with recurrent malignant glioma to assess response rate, survival and effects of treatment. PATIENTS AND METHODS: Ten patients with histologically proven malignant glioma (seven with glioblastoma multiforme (GBM) and three with anaplastic astrocytoma) received SarCNU (860 mg/m(2)) orally on days 1, 5 and 9 on a 6 week schedule. RESULTS: A total of ten patients were treated on protocol before accrual was suspended for a high rate of pulmonary toxicity. Of eight evaluable patients, five demonstrated at least one grade deterioration in DLCO from baseline. This necessitated premature closure of the trial. Stable disease was seen in five of seven evaluable patients (median duration 4.8 months; range 0.8-9.2) with progressive disease in the remainder. CONCLUSION: Despite promising preclinical data, SarCNU caused pulmonary toxicity in patients with recurrent malignant glioma and we plan no further studies in this indication.