Sentinel-Lymph-Node-Based Management or Routine Axillary Clearance? Five-Year Outcomes of the RACS Sentinel Node Biopsy Versus 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 years. METHODS: A total of 1088 women with breast cancer less than 3 cm 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 volume <15%; and (3) subjectively assessed arm morbidity for the domains swelling, symptoms, dysfunction, and disability. Assessments were performed at 1 and 6 months after surgery and then annually. RESULTS: Limb volume increased progressively in the operated and nonoperated arms for 2 years and persisted unchanged to year 5, accompanied by weight gain. Correction by change in the nonoperated arm showed a mean volume increase of 70 mL in the RAC group and 26 mL in the SNBM group (P < 0.001) at 5 years. Only 28 patients (3.3%) had a corrected increase >15% from baseline (RAC 5.0% vs. SNBM 1.7%). Significant predictors were surgery type (RAC vs. SNBM), obesity, diabetes, palpable tumor, and weight gain exceeding 10% of baseline value. CONCLUSIONS: Subjective assessments revealed persisting patient concerns about swelling and symptoms but not overall disability at 5 years. Subjective scores were only moderately correlated with volume increase. SNAC1 has demonstrated that objective morbidity and subjective morbidity persist for 5 years after surgery and that SNBM significantly lowers the risk of both.

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: 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: 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. 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 a 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 was rated as 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.

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.

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.

Congenital epignathus associated with a cleft palate: a case report.

BACKGROUND: Epignathus is a rare, benign, congenital teratoma of the hard palate with an estimated incidence of 1 in 200,000 live births. Epignathus frequently leads to a high mortality (80-100%) due to airway obstruction in the neonatal period. CASE PRESENTATION: We report a case of successful management of a rare oropharyngeal teratoma in a African newborn girl who was referred to our institute with a large protruding intraoral mass, combined with cleft palate, causing some respiratory compromise. The palatal mass was removed on the fifth day after birth, and a palatoplasty performed on day 30. CONCLUSION: Epignathus is a life-threatening condition at the time of delivery. Appropriate management begins with securing the airway, followed by complete resection of the tumor.

A giant fibroadenoma in a mature woman: diagnosis and treatment in a limited resource environment (a case report).

We report an extremely rare case of a 40-year-old woman with a giant fibroadenoma of 30cm in diameter that was accompanied by ulceration and bleeding. We document the onset, the clinical presentation, as well as the challenge encountered in the diagnosis and managing in a limited resource environment.

Multimodal exercise improves quality of life of women being treated for breast cancer, but at what cost? Randomized trial with economic evaluation.

To evaluate the efficacy and economic efficiency of a multimedia, multimodal physical activity program for women undergoing adjuvant therapy following surgery for breast cancer. We conducted a randomized trial with concurrent incremental cost-effectiveness analysis and blinded baseline, 3, 6 and 12-month follow-up assessments amongst women undergoing adjuvant therapy following surgery for breast cancer (n = 89). The intervention was a multimedia, multimodal exercise program comprising strength, balance and endurance training elements. The control was sham flexibility and relaxation program delivered using similar materials. The primary outcome was health-related quality of life (EQ-5D & VAS, EORTC C30, BR23). Economic outcomes included direct health care costs and productivity gains and losses. Participants in the intervention group demonstrated greater improvement in health-related quality of life between baseline and the 3-month assessment [mean (sd) EQ-5D VAS (0-100) baseline: 72.6 (15.6), 3 month: 80.6 (11.6)] when compared to control group participants [baseline: 77.5 (13.5), 3 month: 74.1 (20.6), P = 0.006] and also improved more in terms of physical function [mean (sd) EORTC C30 physical function scale intervention (0-100) baseline: 84.9 (14.8), 3 month: 86.9 (10.7), control baseline: 91.3 (9.6), 3 month: 86.7 (14.9), P = 0.02]. These improvements were not sustained beyond this point. Upper limb volumes were also lower amongst intervention group participants. However, there was low probability that the intervention would be both less costly and more effective than the control condition (range probability = 0.05-50.02% depending on approach). Provision of multimodal exercise programs will improve the short-term health of women undergoing adjuvant therapy for breast cancer but are of questionable economic efficiency.

Comparing patients' and clinicians' assessment of outcomes in a randomised trial of sentinel node biopsy for breast cancer (the RACS SNAC trial).

The RACS sentinel node biopsy versus axillary clearance (SNAC) trial compared sentinel-node-based management (SNBM) and axillary lymph-node dissection (ALND) for breast cancer. In this sub study, we sought to determine whether patient ratings of arm swelling, symptoms, function and disability or clinicians' measurements were most efficient at detecting differences between randomized groups, and therefore, which of these outcome measures would minimise the required sample sizes in future clinical trials. 324 women randomised to SNBM and 319 randomised to ALND were included. The primary endpoint of the trial was percentage increase in arm volume calculated from clinicians' measurements of arm circumference at 10 cm intervals. Secondary endpoints included reductions in range of motion and sensation (both measured by clinicians); and, patients' ratings of arm swelling, symptoms and quality of life, using the European Organisation for Research and Treatment of Cancer Breast Cancer Module (EORTC QLM-BR23), the body image after breast cancer questionnaire (BIBC) and the SNAC study specific scales (SSSS). The relative efficiency (RE, the squared ratio of the test statistics, with 95% confidence intervals calculated by bootstrapping) was used to compare these measures in detecting differences between the treatment groups. Patients' self-ratings of arm swelling were generally more efficient than clinicians' measurements of arm volume in detecting differences between treatment groups. The SSSS arm symptoms scale was the most efficient (RE = 7.1) The entire SSSS was slightly less so (RE = 4.6). Patients' ratings on single items were 3-5 times more efficient than clinicians' measurements. Primary endpoints based on patient-rated outcome measures could reduce the required sample size in future surgical trials.

Participation in the RACS sentinel node biopsy versus axillary clearance trial.

BACKGROUND: The Royal Australasian College of Surgeons (RACS) SNAC trial is a randomized controlled trial of sentinel node biopsy (SNB) versus axillary clearance (AC). It opened in May 2001 and is recruiting rapidly with good acceptance by consumers. METHODS: A study of eligibility and treatment choices was conducted between November 2001 and September 2002 for women presenting with early breast cancer to 10 centres participating in the trial. RESULTS: More than half of the 622 women (54%) were ineligible for trial entry because they had large (> 3 cm) or multicentric cancers. Participation was offered to 92% of eligible women and was taken up by 63%. The commonest reason for not participating was the desire to choose treatment rather than have it randomly allocated. Despite this there is a great acceptance of clinical trials because very few women (4% of those eligible) gave 'lack of interest in clinical trials' as the reason for non-participation. Few women who declined trial participation chose to have SNB alone (4.5% of those eligible). CONCLUSION: Sentinel node biopsy may become the standard of care for managing small breast cancers, but a significant number of patients will still require or choose axillary dissection. Results from large randomized trials are needed to determine the relative benefits and harms of SNB compared with AC. Surgeons must carefully discuss options for management with their patients.

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 µM) significantly stimulated the proliferation of brown preadipocytes and reduced that of white preadipocytes. During differentiation, dexamethasone (at 0.1, 1, and 10 µM) 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.

Identification of the sentinel lymph node in the SNAC-1 trial.

BACKGROUND: A combination of scintigraphy and a lymphotropic dye (patent blue dye (BD)) is the recommended technique to detect the sentinel lymph node (SLN) in early breast cancer. This study determined the effect of clinical factors on SLN identification in the sentinel node biopsy versus axillary clearance (SNAC) trial. METHODS: A total of 1088 women were registered. Lymphatic mapping was performed using preoperative lymphoscintigraphy (LSG) and gamma probe (GP) combined with peritumoural injection of patent BD (971 patients) or BD alone (106 patients). RESULTS: SLNs were identified in 1024 women (94%), localized with LSG in 779 (81.4%), and were identified by GP in 879 (91.8%). The BD identified SLNs in 890 of 1073 (82%) women. Three patients had allergic reactions. BD detected the SLNs in 141 of 178 women with negative LSG mapping and in 44 of 79 women with no hot SLNs detected intraoperatively. Age, body mass index (BMI) and tumour presentation (screen detected versus symptomatic) were significantly related to the identification of the SLN. For BD, the primary tumour location was significantly related to identification rate. The detection of blue SLN was significantly lower in women with inner quadrant tumours. CONCLUSION: The combined technique resulted in a high identification rate. BD contributed to the identification of the SLNs in patients where LSG and GP failed to identify the sentinel node. Special attention to these techniques is needed in particular groups of patients such as those with high BMI, screen-detected primary tumours and tumour located in the inner quadrants.

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.

Sentinel node biopsy and large (≥3 cm) breast cancer.

BACKGROUND: Sentinel node biopsy is an accurate method for staging the axilla in early (small) breast cancers. However, data for the role of this technique for large breast cancers remain limited. METHOD: From the Royal Adelaide Hospital Sentinel Node database and the SNAC trial database, 100 subjects were identified with clinically node negative, large (≥3 cm) primary breast cancer who had undergone sentinel node biopsy and immediate axillary clearance. The pathology results from the sentinel node and axillary specimens were analysed. RESULTS: Average tumour size was 3.91 cm (range 3-10 cm) and 65 of 100 cases had metastatic disease in the axillary nodes. A sentinel node was successfully identified in 93 out of 100 cases with an average of 1.75 sentinel nodes sampled. Sixty-two per cent (58 out of 93) were sentinel node positive and 43% (43 out of 100) had a positive non-sentinel node. The false negative rate following successful sentinel node identification was 4.9% (3 out of 61). CONCLUSION: Sentinel node biopsy was an accurate tool for staging the axilla with a false negative rate comparable to that seen in small tumours. However, given the increased incidence of metastases with larger cancers, further prospective investigation is warranted.

Evaluation of implementation of sentinel node biopsy in Australia.

BACKGROUND: Sentinel node biopsy (SNB) has been a major change in surgical technique for the management of early breast cancer. In June 2008, the National Breast and Ovarian Cancer Centre (NBOCC) released evidence-based guidelines for the use of SNB in Australia. During 2010, NBOCC undertook a cohort study to identify the extent to which clinical practice in Australia reflected the recommendations for use of SNB in the 6 months after release of the guidelines. METHODS: Records obtained from four datasets, Royal Australasian College of Surgeons National Breast Cancer Audit, New South Wales Central Cancer Registry, Victorian Cancer Registry and Medicare Benefits Schedule records, were analysed to determine the extent to which the four key guideline recommendations had been implemented. This was supplemented by an audit of written SNB protocols of a sample of pathology laboratories in Australia. RESULTS: ACROSS all cohorts, between 78 and 83% of women in Australia with tumours ≤3 cm had an SNB. Data were not available to indicate whether nodes were clinically negative. The likelihood of women having an SNB decreased outside the metropolitan regions, for women treated as public patients compared with private patients and as the size of the tumour increased. In 90% of procedures both preoperative lymphoscintigraphy with isotope and blue dye were used. CONCLUSION: The findings from the study confirm that best practice recommendations from the NBOCC guidelines for SNB were largely being implemented for women with early breast cancer in Australia within 6 months of their release.

Psychosocial impact of newly diagnosed advanced breast cancer.

The purpose of this study was to delineate the key emotional concerns of women newly diagnosed with recurrent or metastatic breast cancer. Sixty-six women diagnosed with metastatic breast cancer within the previous 6 months, receiving treatment at the Medical Oncology Departments of two metropolitan teaching hospitals, completed measures of HADS, IES, CARES-SF and Memorial Symptom Assessment Scale, and participated in a semi-structured interview. There were high levels of psychological morbidity, 56.7% of women younger than 55 years qualifying as "cases" on the HADS, compared with 34.5% of women aged over 55 years. The total HADS score was significantly correlated with the Global and Physical Subscales of the MSAS and CARES. Women younger than 55 years had significantly higher levels of intrusive and avoidant symptoms than women over 55 years. Women also reported high numbers of physical symptoms. Key themes which emerged during the interviews were: difficulties in communicating with doctors, perceived delay in diagnosis, the emotional impact, concerns about the family, feelings about why the cancer developed, other life stress and trauma, and use of non-prescribed treatments.