乳腺癌前哨淋巴结乳腺癌前哨淋巴结与放疗与放疗保乳手术保乳手术breast conservative treatment (BCT) safe- results of randomized trials in the 1980spatients with early breast cancer前哨淋巴结活检前哨淋巴结活检a high level accuracyfalse negative rate around 7%equivalent oncological outcomes in terms of distant disease-free and overall survivalsurprisingly low regional recurrence rate of less than 1%前哨淋巴结活检前哨淋巴结活检negative SN-completion ALND is not required前哨淋巴结活检前哨淋巴结活检axillary metastasis are limited the SN in 60-70% overall 90% for low volume involvement (micrometastasis/isolated tumour cells detected by immunohistochemical staining only)前哨淋巴结活检前哨淋巴结活检patients with involved SN omit the completion ALNDno apparent detriment to oncological outcomesACOSOG-Z0011ACOSOG-Z0011American College of Surgeons Oncology Group (ACOSOG)-Z0011axillary dissection vs. no axillary dissection ACOSOG-Z0011ACOSOG-Z0011May 1999-Dec 2004 115 sitesACOSOG-Z0011ACOSOG-Z0011Eligibility criteria older than 18 years,T1-2invasive breast cancer,no palpable axillary adenopathy, and 1 or 2 SN metastasis without extranodal extension ACOSOG-Z0011ACOSOG-Z0011Exclusion criteria Clinically node positive disease more than 2 positive sentinel nodes, matted nodes, gross extranodal diseasePreoperative systemic treatmentsisolated tumour cells (ITC) in the SN ACOSOG-Z0011ACOSOG-Z0011Stratification age (younger or older than 50 years)ER statustumour size (2 cm)ACOSOG-Z0011ACOSOG-Z0011BCS and SNBSN metastasis in 1 or 2 nodes randomly assigned ALND or no further axillary ALND a dissection of at least 10 lymph WBI Systemic adjuvant therapyACOSOG-Z0011ACOSOG-Z0011The main outcome measure overall survivalSecondar youtcome measure disease free survivalACOSOG-Z0011ACOSOG-Z0011noninferiority trial the SNB-only group having a 5-year OS not less than 75% of ALND groupTargeted enrolment was 1900 women with a final analysis after 500 deaths.ACOSOG-Z0011ACOSOG-Z0011The trial was closed 891 patients due to lower than expected accrual and event ratesACOSOG-Z0011ACOSOG-Z0011445 ALND446 SN biopsy alone35 patients (25 on the ALND arm and 10 on the SNB arm) excluded because withdrew consentACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011ACOSOG-Z0011limited SN metastatic breast cancer Breast conservation and systemic therapy, SNB alone compared with ALND did not result in inferior survivalACOSOG-Z0011ACOSOG-Z0011Potential problems statistical design and interpretationenrolment of patientsimbalances between the treatment groups and missing dataACOSOG-Z0011ACOSOG-Z0011The planned target accrual 1900 patients -a prediction of an overall survival rate of 80% at 5 years for women with optimally treated node-positive breast cancerThe study had a slow accrual (115 sites over 4 years leading to 900 patients e some centres entered less than 3 patients which is not many per site), was unable to complete enrolment, and therefore closed early with less than 50% of the targeted accrual and with lower-than-expected event ratesACOSOG-Z0011ACOSOG-Z0011a significant amount of missing data 98 cases (11%) -the number of lymph node metastases was missing,217 cases (32%) -tumour grade was missing20 cases (2%) -tumour size was missing 81 cases(9%) - receptor status was missingThe size of the SN metastasis was unknown in 125 cases (15%),33 cases (4%) had no lymph node metastases15 cases in the SN arm had more than 2 nodes involvedACOSOG-Z0011ACOSOG-Z001127% patients in the ALND arm had further positive nodesThus 27% of the 388 patients in the SNB arm may have had undissected diseaseMacrometastases in the SN 62.5% of patients in the ALND group 55.2% of patients in the SNB group.ACOSOG-Z0011ACOSOG-Z0011This statistically significant imbalancebetween the groups raises the question the SNB group had less tumour burden in their nodes and, consequently, a more favourable prognosisthe axillary recurrence rate was double in the SNB group(0.9% vs. 0.5%)ACOSOG-Z0011ACOSOG-Z0011The most critical issue - eligibility criteria included patients over 18 years old with tumour 5cmwithmacrometastases in2 sentinel nodesthe patients recruited to the study were generally low risk cancersThe majority of patients had small (T1)ER positive invasive ductal carcinomasover 50 years oldraising the questionmany patients with cancers that would have met the eligibility criteria but were not represented in the cohort of patients in the trial.ACOSOG-Z0011ACOSOG-Z0011Another concern the high proportion of patients lost to follow-up 21% ALND and 17% SNACOSOG-Z0011ACOSOG-Z0011WBI with opposing standard tangential fieldsthe fields were not uniform between the randomization armsthe radiation oncologists not blinded前哨淋巴结活检微转移前哨淋巴结活检微转移Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 2301)a phase 3 randomised controlled trialIBCSG 2301IBCSG 2301no axillary dissection non-inferior to axillary dissection one or more micrometastatic (2 mm) sentinel nodes tumour of maximum 5 cmone or more micrometastatic (2 mm) sentinel lymph nodes with no extracapsular extensionIBCSG 2301IBCSG 2301randomly assigned (in a 1:1 ratio) Randomisation was stratified by centre and menopausal statusTreatment assignment was not maskedIBCSG 2301IBCSG 2301primary endpoint disease-free survivalNon-inferiority as a hazard ratio (HR) of less than 1.25 for no axillary dissection versus axillary dissectionThe analysis - intention to treatIBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301IBCSG 2301Analysis of subgroups defined by tumour size, OR, Analysis of subgroups defined by tumour size, OR, PR, tumour grade, and type of surgery PR, tumour grade, and type of surgery Multivariable proportional-hazards regression Multivariable proportional-hazards regression analysis of disease-free survivalanalysis of disease-free survivalIBCSG 2301IBCSG 2301This trial and ACOSOG Z0011-change clinical practice, sparing many patients with early breast-cancer axillary dissectionthe sentinel node is minimally involved thus reducing surgical complications Axillary dissection with no adverse effect on survivalIBCSG 2301IBCSG 2301the 2021 St Gallen Consensus Conference recommending that micrometastases in a single sentinel node should not be an indication for axillary dissection