Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial.

BACKGROUND: For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. METHODS: In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. FINDINGS: Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five [corrected] regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. INTERPRETATION: Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. FUNDING: None.

Factors influencing sentinel lymph node identification failure in breast cancer surgery.

The purpose of this study was to investigate potential risk factors for failed sentinel lymph node identification in breast cancer surgery. Patient characteristics, tumour characteristics, surgeon experience and detection success/failure were registered at 748 sentinel lymph node biopsy procedures at our inpatient clinic. Data were analysed with backward stepwise multiple logistic regression with a cut-off point of p<0.05. We found that increased age, increased BMI, medial tumour location and less surgeon experience independently were associated with a lower sentinel lymph node detection rate. Tumour size, palpability and biopsy method were not significantly associated with the sentinel lymph node detection rate. In conclusion, it is possible to identify patients with a higher risk of sentinel lymph node identification failure and we recommend that these patients are operated by experienced surgeons in order to avoid accumulation of independent risk factors in individual cases.

Organized nation-wide implementation of sentinel lymph node biopsy in Denmark.

Prior to the initiation of a nationwide study of the sentinel node staging technique the Danish Breast Cancer Cooperative Group (DBCG) defined a set of minimum requirements to be met by surgical departments before they could include patients in the study. The requirements specified a minimum patient load in the individual surgical unit, a minimum surgical training in the sentinel node biopsy technique and a minimum quality outcome in a validating learning series of SNLB procedures. A working group assisted departments in meeting these terms and later audited and certified departments before they could include patients into the study. As a result of this strategy the sentinel lymph node staging was fully implemented in all Danish surgical breast cancer centres within three years and all sentinel node biopsies in the period were recorded in the DBCG data centre. Furthermore, the strategy accelerated the ongoing process of centralizing breast surgery in specialized departments.

Diagnostic challenges in clinical, radiological and histopathological tests regarding papillomatous lesions of the breast.

Papillomas of the female breast is a relatively frequent lesion, and the majority are benign when excised. However, some may host malignant or premalignant areas. Consequently, it is a worldwide accepted principle to excise the lesion whenever diagnosed. However, this leads to a large number of patients having an unnecessary operation. The present study was designed to investigate whether we could find clinical, radiological and pathological factors in the preoperative, diagnostic setting that could identify patients hosting a benign papilloma in order to avoid operation. The patient material consisted of 260 patients, all with a preoperative diagnosis of a papillomatous process in core biopsy. The lesion was excised, and 71% had a benign lesion. The rest had lesions ranging from premalignant to malignant. In the clinical, radiological and histopathological investigations conducted, we were not able to identify factors that statistically significant could predict whether the lesion was benign or malignant. However, our data showed a higher prevalence of malignant and premalignant lesions for older patient, larger lesions, and lesions found at a longer distance from the papilla. We conclude that, since almost 30% of the patients in our study ended up with a premalignant or malignant diagnosis, where no statistically significant preoperative factors could indicate a benign outcome, operation is warranted in all patients with a preoperative diagnosis of a papillomatous lesion.

Mastectomy using ultrasonic dissection: effect on seroma formation.

Seroma formation is the most common complication after mastectomy. Among the several known etiological factors the surgical procedure used may be of importance for seroma formation. This prospective study was carried out to evaluate the ultrasonic energy dissection technique and its effect on seroma formation and other complications: 59 patients with operable breast cancer underwent modified radical mastectomy, performed in 30 of them with an Ultracision Harmonic scalpel and in 29 with scissors and electrocautery. In all cases a standard level II axillary dissection was performed with scissors. We found no differences in the outcome of surgery. Peroperative bleeding (median 300 ml, range 100-790 vs 300 ml, range 40-1400), drain volume (585 ml, range 130-1455) vs 645 ml, range 95-1570), seroma formation 50 (0-580) ml vs 105 (0-3775) ml and wound complications were about the same in both groups. In conclusion, neither clinical advantages or disadvantages of the ultrasound dissection technique were found.

[Anaphylactic reaction to patent blue in sentinel node biopsy]. / Anafylaktisk reaktion på "patent blue" ved "sentinel node"-biopsi for brystkraeft.

Three cases of anaphylactic reactions to patent blue used during sentinel lymph node biopsy are presented. One of the cases was serious. We also give recommendations for treatment of this complication.

[Sentinel lymph node biopsy and breast cancer]. / Sentinel node ved cancer mammae.

After implementation of the sentinel lymph node biopsy technique as a standard procedure in the treatment of breast cancer the indications and technique used has changed. This review gives a brief, comprehensive update of the method regarding surgical techniques, histopathology, morbidity, recurrence and mortality.

[Four years of experience with sentinel node biopsy for breast cancer]. / Fire års erfaringer med sentinel node-operation ved brystcancer.

INTRODUCTION: The sentinel node (SN) procedure is increasingly being employed in breast surgery to determine the status of the axilla. So far, experience has shown that determination of axillary status is just as accurate as with axillary dissection. Results from 47 months of prospective registration of SN operations are presented here. MATERIALS AND METHODS: From 1 February 2001 to 31 December 2004, SN was performed on 838 patients, constituting 62.6% of the patients treated for primary breast cancer. SNs were detected using two tracers. Primary axillary dissection was performed when no SN was detected. Perioperative investigation of SN was done by frozen section microscopy. If a positive SN was detected, axillary dissection was performed during the same operation. If metastasis was detected only by paraffin microscopy, axillary dissection was performed during a later operation. RESULTS: SN was detected in 91.2% of the patients. This rate increased significantly during the period. 86 of the patients (25.0%) showing metastasis to SN had false negative results at frozen section microscopy. Of these, 75 had axillary dissection performed at a later operation. In 50 patients (6.0%), an extra-axillary lymph node was removed, changing the staging in 3 cases (0.4%). In 3 cases, a positive axillary lymph node was detected after negative SN within the observation period. CONCLUSION: This study showed that we are on a par with international standards for SN procedure. We believe that the degree of the surgeon's experience has a great impact on the rate of detection. We feel that continuous quality control is necessary, so that measures can be taken if and when standards are not fulfilled.