Sentinel-lymph-node-based management or routine axillary clearance? Three-year outcomes of the RACS Sentinel Node Biopsy versus Axillary Clearance (SNAC) 1 trial

Purpose We sought to determine whether the benefits of sentinel-node-based management (SNBM) over routine axillary clearance (RAC) at 1 year persisted to 3 years of follow-up. Methods 1088 women with clinically node negative breast cancer were randomly assigned to SNBM versus RAC. Upper limb volume, symptoms and function were assessed at 1, 6, 12, 24 and 36 months after surgery objectively with upper limb measurements by clinicians, and subjectively by patients’ using validated self-rating scales. Results Upper limb volume increased in both groups over the first 2 years and differed between the two groups all time points beyond 1 month (P<0.02), but then plateaued. Upper limb swelling was no worse in women who had axillary clearance as two-stage procedure than in women assigned RAC as a one-stage procedure. Upper limb volume had increased 15% or more in 6.0% at 6 months and 17.6% at 3 years in those assigned RAC versus 4.2% and 11.9% in those assigned SNBM. Reductions in upper limb movement were also greater with RAC than SNBM over 6 months, but improved and were similar in the two groups from 1 to 3 years. Subjective ratings of upper limb swelling, symptoms, dysfunction, and disability over 3 years were worse in the RAC group. Upper limb swelling at 3 years was rated severe by few women (1.1%), but moderate by 9.4% in the RAC group and 2.5% in the SNBM group (P<0.001). Conclusions The benefits of SNBM over RAC persist 3 years after surgery.Royal Australasian College of Surgeon

Sentinel node biopsy for breast cancer: Using local results for estimation of risk to the patient

Background: Sentinel node biopsy (SNB) is being increasingly used but its place outside randomized trials has not yet been established. Methods: The first 114 sentinel node (SN) biopsies performed for breast cancer at the Princess Alexandra Hospital from March 1999 to June 2001 are presented. In 111 cases axillary dissection was also performed, allowing the accuracy of the technique to be assessed. A standard combination of preoperative lymphoscintigraphy, intraoperative gamma probe and injection of blue dye was used in most cases. Results are discussed in relation to the risk and potential consequences of understaging. Results: Where both probe and dye were used, the SN was identified in 90% of patients. A significant number of patients were treated in two stages and the technique was no less effective in patients who had SNB performed at a second operation after the primary tumour had already been removed. The interval from radioisotope injection to operation was very wide (between 2 and 22 h) and did not affect the outcome. Nodal metastases were present in 42 patients in whom an SN was found, and in 40 of these the SN was positive, giving a false negative rate of 4.8% (2/42), with the overall percentage of patients understaged being 2%. For this particular group as a whole, the increased risk of death due to systemic therapy being withheld as a consequence of understaging (if SNB alone had been employed) is estimated at less than 1/500. The risk for individuals will vary depending on other features of the particular primary tumour. Conclusion: For patients who elect to have the axilla staged using SNB alone, the risk and consequences of understaging need to be discussed. These risks can be estimated by allowing for the specific surgeon's false negative rate for the technique, and considering the likelihood of nodal metastases for a given tumour. There appears to be no disadvantage with performing SNB at a second operation after the primary tumour has already been removed. Clearly, for a large number of patients, SNB alone will be safe, but ideally participation in randomized trials should continue to be encouraged

Effects of glucocorticoids on human brown adipocytes

Clinical cases of glucocorticoid (GC) excess are characterized by increased fat mass and obesity through the accumulation of white adipocytes. The effects of GCs on growth and function of brown adipose tissue are unknown and may contribute to the negative energy balance observed clinically. This study aims to evaluate the effect of GCs on proliferation, differentiation, and metabolic function of brown adipocytes. Human brown adipocytes sourced from supraclavicular fat biopsies were grown in culture and differentiated to mature adipocytes. Human white adipocytes sourced from subcutaneous abdominal fat biopsies were cultured as controls. Effects of dexamethasone on growth, differentiation (UCP1, CIDEA, and PPARGC1A expression), and function (oxygen consumption rate (OCR)) of brown adipocytes were quantified. Dexamethasone (1 mu M) significantly stimulated the proliferation of brown preadipocytes and reduced that of white preadipocytes. During differentiation, dexamethasone (at 0.1, 1, and 10 mu M) stimulated the expression of UCP1, CIDEA, and PPARGC1A in a concentration-dependent manner and enhanced by fourfold to sixfold the OCR of brown adipocytes. Isoprenaline (100 nM) significantly increased (P < 0.05) expression of UCP1 and OCR of brown adipocytes. These effects were significantly reduced (P < 0.05) by dexamethasone. Thus, we show that dexamethasone stimulates the proliferation, differentiation, and function of human brown adipocytes but inhibits adrenergic stimulation of the functioning of brown adipocytes. We conclude that GCs exert complex effects on development and function of brown adipocytes. These findings provide strong evidence for an effect of GCs on the biology of human brown adipose tissue (BAT) and for the involvement of the BAT system in the metabolic manifestation of Cushing's syndrome

Sentinel Lymph Node Based Management or Routine Axillary Clearance? Three-year Outcomes of the RACS Sentinel Node Biopsy Versus Axillary Clearance (SNAC) 1 Trial

Methods: A total of 1,088 women with clinically node-negative breast cancer were randomly assigned to the SNBM or RAC group. Upper limb volume, symptoms, and function were assessed at 1, 6, 12, 24, and 36 months after surgery objectively with upper limb measurements by clinicians and subjectively by patients’ using validated self-rating scales

"not Just Following What Doctors Say": piloting of a Decision aid for women considering participation in the Sentinel Node Biopsy versus Axillary Clearance 2 (Snac2) trial

Aims. Suboptimal understanding of clinical trial-related information may not only compromise accrual, but also the informed consent process. Decision aids (DAs) enhance patient understanding and decision-making in treatment and screening settings, but only one previous trial has formally evaluated DA use in the clinical trial setting. A DA for the Sentinel Node versus Axillary Clearance (SNAC2) trial was developed to help eligible women with a recent diagnosis of breast cancer to decide between: 1) a more invasive, standard treatment with known potential side-effects, or 2) a randomised trial comparing option 1 to a less invasive treatment with fewer side-effects but a possible small, but higher risk of local recurrence. The pilot aimed to obtain evidence on the acceptability, utility and feasibility of the DA in routine trial clinical practice for women considering participation in the SNAC2 trial. Methods. The DA was developed according to International Patient Decision Aid Standards (IPFAS) and discussions with key stakeholders. Twenty women eligible to participate in the SNAC2 trial in New Zealand completed questionnaires assessing: information and involvement preferences, decisional conflict, understanding and attitudes towards SNAC2, anxiety, and general DA feedback. A follow-up telephone interview elicited more detailed feedback about the DA's design, clarity and utility, and assessed women's knowledge about, and attitudes towards SNAC2. Results. Participants indicated good subjective and objective understanding of SNAC2 and reported low decisional conflict and anxiety. They found the DA booklet was helpful when deciding about trial participation; facilitated understanding of the standard information sheet; and provided additional, useful information to the standard trial information sheet. Conclusions. Findings suggest that the DA provided a resource that women found acceptable and helpful in assisting decision-making about SNAC2 trial participation. The pilot process and findings support the generalisability and applicability of the trial DA design to other clinical trial settings

Development and piloting of a decision aid for women considering participation in the Sentinel Node Biopsy versus Axillary Clearance 2 breast cancer trial

Background/aims: This study aimed to (1) develop a decision aid for women considering participation in the Sentinel Node Biopsy versus Axillary Clearance 2 (SNAC-2) breast cancer surgical trial and (2) obtain evidence on its acceptability, feasibility, and potential efficacy in routine trial clinical practice via a two-stage pilot. Methods: The decision aid was developed according to International Patient Decision Aid Standards. Study 1: an initial pilot involved 25 members of the consumer advocacy group, Breast Cancer Network Australia. Study 2: the main pilot involved 20 women eligible to participate in the SNAC-2 trial in New Zealand. In both pilots, a questionnaire assessed: information and involvement preferences, decisional conflict, SNAC-2 trial-related understanding and attitudes, psychological distress, and general decision aid feedback. A follow-up telephone interview elicited more detailed feedback on the decision aid design and content. Results: In both pilots, participants indicated good subjective and objective understanding of SNAC-2 trial and reported low decisional conflict and anxiety. The decision aid was found helpful when deciding about trial participation and provided additional, useful information to the standard trial information sheet. Conclusion: The development and two-stage piloting process for this decision aid resulted in a resource that women found very acceptable and helpful in assisting decision-making about SNAC-2 trial participation. The process and findings provide a guide for developing other trial decision aids

Sentinel-lymph-node-based management or routine axillary clearance? Five-year outcomes of the RACS sentinel node biopsyversus axillary clearance (SNAC) 1 trial: assessment and incidence of true lymphedema

Purpose: To determine whether the benefits of sentinel-node-based management (SNBM) over routine axillary clearance (RAC) persisted to 5\ua0years. Methods: A total of 1088 women with breast cancer less than 3\ua0cm in diameter and clinically negative axillary nodes were randomized to SNBM with axillary clearance if the sentinel node was positive or RAC preceded by sentinel-node biopsy. The outcomes were: (1) objectively measured change in the volume of the operated and contralateral nonoperated arms; (2) the proportion with an increase in arm volum

10-Year axillary recurrence in the RACS SNAC1 randomised trial of sentinel lymph node-based management versus routine axillary lymph node dissection

Background: Sentinel node-based management (SNBM) is the international standard of care for early breast cancer that is clinically node-negative based on randomised trials comparing it with axillary lymph node dissection (ALND) and reporting similar rates of axillary recurrence (AR) without distant disease. We report all ARs, overall survival, and breast cancer-specific survival at 10-years in SNAC1. Methods: 1.088 women with clinically node-negative, unifocal breast cancers 3 cm or less in diameter were randomly assigned to either SNBM with ALND if the sentinel node (SN) was positive, or to SN biopsy followed by ALND regardless of SN involvement. Results: First ARs were more frequent in those assigned SNBM rather than ALND (11 events, cumulative risk at 10-years 1·85%, 95% CI 0·95–3.27% versus 2 events, 0·37%, 95% CI 0·08–1·26%; HR 5·47, 95% CI 1·21–24·63; p = 0·013). Disease-free survival, breast cancer-specific survival, and overall survival were similar in those assigned SNBM versus ALND. Lymphovascular invasion was an independent predictor of AR (HR 6·6, 95% CI 2·25–19·36, p < 0·001). Conclusion: First ARs were more frequent with SNBM than ALND in women with small, unifocal breast cancers when all first axillary events were considered. We recommend that studies of axillary treatment should report all ARs to give an accurate indication of treatment effects. The absolute frequency of AR was low in women meeting our eligibility criteria, and SNBM should remain the treatment of choice in this group. However, for those with higher-risk breast cancers, further study is needed because the estimated risk of AR might alter their choice of axillary surgery