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.

Australasian experience and trials in sentinel lymph node biopsy: the RACS SNAC trial.

PURPOSE: Sentinel lymph node biopsy (SLNB) has been rapidly adopted by surgical oncologists in the management of invasive breast cancer. This study reviews the Royal Australasian College of Surgeons (RACS) Sentinel Node versus Axillary Clearance (SNAC) trial and reports an interim analysis of the first 150 subjects. Other currently open multi-institutional randomized trials in SLNB are reviewed. METHODS: The SNAC trial is a multicentre, centrally randomized, phase III clinical trial. Subjects are randomized to SLNB alone (with completion axillary clearance, AC, for sentinel node-positive patients) or AC plus SLNB, with stratification according to age (< 50 years, more than or equal to 50 years), primary tumour palpability (palpable vs impalpable), lymphatic mapping technique (blue dye plus scintigraphy vs blue dye alone) and centre. RESULTS: The trial was launched in May 2001 in two centres. Randomization continues currently at the rate of approximately 30 subjects per month (total, 1,012 at the time of writing) from 32 participating centres in Australia and New Zealand. Data from the first 150 subjects have been analysed to assess: compliance with randomized treatment allocation; measures of test performance for SLNB (detection, removal, sensitivity, specificity and false-negative rates); measures of arm volume, function, symptoms and quality of life; and sample size estimates. CONCLUSIONS: The SNAC trial is one of the fastest accruing clinical trials in Australasia. It is on track to determine whether differences in morbidity, with equivalent cancer-related outcomes, exist between SLNB and AC for women with early breast cancer.

Is the one-step nucleic acid amplification assay better for intra-operative assessment of breast sentinel nodes?

BACKGROUND: Intra-operative assessment of sentinel lymph nodes in breast cancer offers the opportunity to prevent two-stage surgical procedures. At our institution we employ touch imprint cytology (TIC), which lacks sensitivity. In this study we compare the one-step nucleic acid amplification (OSNA) assay to TIC. METHODS: Imprints were taken from 63 lymph nodes from 35 patients. The lymph nodes were sectioned at 2-mm intervals and alternate slices submitted for either histology or OSNA assay, with histology as the reference standard. RESULTS: Seven patients were histologically positive. Nine and five patients were positive by OSNA and TIC, respectively. Sensitivity, specificity, positive and negative predictive value for the OSNA assay were 85.7%, 85.7%, 63.6% and 96.6% and for TIC were 70.0%, 96.6%, 87.5% and 90.3%. CONCLUSION: In this study OSNA had a higher sensitivity than TIC. Fewer patients assessed by the OSNA assay would have required a two-stage procedure. The OSNA assay appears to be a highly cost-effective method for providing rapid and reliable intra-operative assessment of sentinel lymph nodes.

Intraoperative imprint cytology for breast cancer sentinel nodes: is it worth it?

BACKGROUND: Re-operative surgery is stressful for patients and is an additional burden to an already stretched public health system. Intraoperative confirmation of breast cancer metastases in sentinel lymph nodes (SLNs) provides the necessary information for the surgeon to proceed with immediate axillary dissection, avoiding the need for a second operation, its associated cost, morbidity and adjuvant treatment delays. Our challenge was to implement a technique that was rapid, inexpensive and had a negligible false positive rate. The aim of this study was to determine whether touch imprint cytology (TIC) could reduce returns to theatre without compromising patient safety and pathology department and operating theatre efficiency. METHODS: Intraoperative TIC was performed on bisected SLNs from 134 patients. Post-operatively, specimens were examined as haematoxylin and eosin-stained, paraffin-embedded 2-mm sections. Further sectioning and immunohistochemisty was performed on negative SLNs. RESULTS: The sensitivity of TIC for metastases was 23.8%, the specificity was 100% and the accuracy was 76.1%. Ten patients with macrometastases and none with micrometastastes were detected intraoperatively. The sensitivity of TIC for detecting macrometastases was 34.5%, the accuracy was 78.4% and the specificity was 100%. CONCLUSION: Ten patients avoided a subsequent surgery. The technique caused no theatre delays and the minimal cost was compensated for by the avoidance of a second procedure for a third of patients who definitively required axillary clearance. No patients had an unnecessary axillary clearance and no patients with micrometastases or isolated tumour cells were subjected to an immediate axillary clearance. It would be justifiable to continue this simple, low-cost and non-disruptive approach.

Factors affecting the preoperative and postoperative extracellular fluid in the arm on the side of breast cancer: a cohort study.

BACKGROUND: To explore what factors affect volume of extracellular fluid (ECF) in the arm on the side of surgery pre- and postoperatively and to determine the value of knowing preoperative ECF volume for diagnosis of lymphedema postoperatively. METHODS AND RESULTS: Women (N=516) with early breast cancer were assessed preoperatively and within 4 weeks postoperatively. Baseline measures included inter-arm ECF ratio, side of cancer, number of nodes involved, and other individual characteristics. Postoperative assessment included inter-limb ECF ratio and details from surgery. The postoperative ECF ratio was categorized as to whether it exceeded previously established thresholds, and the change in ECF was categorized as to whether it exceeded 0.1. Linear regression identified which factors explained the variance for preoperative ECF ratio and the change in ratio. Chi square analysis compared whether women categorized using thresholds were the same as those whose ratio increased >0.1 postoperatively. Postoperative ECF ratio was significantly higher than the preoperative ratio (p<0.001). Women whose ECF ratio exceeded previously established thresholds were not the same as those whose ratio increased >0.1 postoperatively (p<0.001). Only the side of surgery explained the preoperative ECF measure; extent of surgery and actual weight explained the change in ECF ratio. CONCLUSION: The ECF ratio preoperatively is not affected by nodal involvement. The change in ECF ratio is affected by the extent of surgery and body mass. Change from preoperative ECF ratio did identify more women at risk for lymphedema than reliance postoperatively on thresholds, supporting preoperative measures.

Internal mammary sentinel nodes: ignore, irradiate or operate?

INTRODUCTION: This study describes the results of internal mammary chain (IMC) biopsy, identifying factors that predict 'hot spots' and nodal metastases for patients in whom mapped IMC nodes were routinely dissected. METHODS: The nodal basin and status of every axillary and IMC site identified by lymphoscintigraphy were examined. Binary logistic regression analysed the relationship of several patients and tumour factors with IMC hot spots and metastases. RESULTS: Ninety of 490 patients (18.4%) had IMC sentinel lymph nodes (SLNs) identified by lymphatic mapping and dissected, and 20 of these (22.2%) were found to have metastases. Mapping to the IMC was most likely for women aged under 35 years (29.4%) (p=0.117), women aged 35-44 (22.6%) (p=0.034) or those with medial (23.7%) or central tumour location (22.2%) (p=0.014; p=0.062, respectively). Predictors of IMC positivity included age <35 years (p=0.063), grade 3 histology (p=0.018) and lymphatic vascular invasion (LVI) (p=0.032). Although IMC positivity was more likely with positive axillary nodes, this trend was not significant. CONCLUSION: We identified several factors (age <35 years, tumour grade and LVI) that independently predict IMC SLN identification and positivity for patients with stage I or II breast cancer. Where IMC hot spots are not dissected, we predict IMC positivity of 50% or more for young women (<35 years) or women with high grade or LVI positive tumours, and these women may benefit from more intensive chemotherapy and radiotherapy to the IMC.

Phytoestrogens and indicators of breast cancer prognosis.

Breast cancer incidence is lower and survival is longer in Asian women residing in Japan, China, or the Philippines than Caucasian women residing in the United States. Phytoestrogen intake has been examined as a possible reason for the disparity in breast cancer incidence and survival. This study examined the association between phytoestrogen intake prior to diagnosis of breast cancer and indicators of breast cancer prognosis (tumor size, estrogen and progesterone receptor status, histological grade, lymphovascular invasion, nodal spread, and stage) in 128 women, aged 40-79 yr, newly diagnosed with invasive breast cancer. After controlling for significant confounding factors, higher intakes of phytoestrogens were associated with favorable indicators of breast cancer. In women with higher intakes of phytoestrogens, there was a 32% reduction in the odds of being diagnosed with any stage of cancer other than stage 1 (95% confidence interval, CI = 0.49-0.93; P = 0.02), a 38% reduction in odds of being diagnosed with positive lymphovascular invasion (95% CI = 0.40-0.95; P = 0.03), and a 66% increase in the odds of being diagnosed with a positive progesterone receptor (95% CI = 1.06-2.58; P = 0.03). We conclude that phytoestrogen intake prior to diagnosis may improve prognosis of breast cancer.