Bromham Nathan, Schmidt-Hansen Mia, Astin Margaret, Hasler Elise, Reed Malcolm W
National Guideline Alliance, Royal College of Obstetricians and Gynaecologists, 27 Sussex Place, Regents Park, London, England, UK, NW1 4RG.
Centre for Academic Primary Care, School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, UK, BS8 2PS.
Cochrane Database Syst Rev. 2017 Jan 4;1(1):CD004561. doi: 10.1002/14651858.CD004561.pub3.
Axillary surgery is an established part of the management of primary breast cancer. It provides staging information to guide adjuvant therapy and potentially local control of axillary disease. Several alternative approaches to axillary surgery are available, most of which aim to spare a proportion of women the morbidity of complete axillary dissection.
To assess the benefits and harms of alternative approaches to axillary surgery (including omitting such surgery altogether) in terms of overall survival; local, regional and distant recurrences; and adverse events.
We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, Pre-MEDLINE, Embase, CENTRAL, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov on 12 March 2015 without language restrictions. We also contacted study authors and checked reference lists.
Randomised controlled trials (RCTs) including women with clinically defined operable primary breast cancer conducted to compare axillary lymph node dissection (ALND) with no axillary surgery, axillary sampling or sentinel lymph node biopsy (SLNB); RCTs comparing axillary sampling with SLNB or no axillary surgery; RCTs comparing SLNB with no axillary surgery; and RCTs comparing ALND with or without radiotherapy (RT) versus RT alone.
Two review authors independently assessed each potentially relevant trial for inclusion. We independently extracted outcome data, risk of bias information and study characteristics from all included trials. We pooled data according to trial interventions, and we used hazard ratios (HRs) for time-to-event outcomes and odds ratios (OR) for binary outcomes.
We included 26 RCTs in this review. Studies were at low or unclear risk of selection bias. Blinding was not done, but this was only considered a source of bias for outcomes with potential for subjectivity in measurements. We found no RCTs of axillary sampling versus SLNB, axillary sampling versus no axillary surgery or SLNB versus no axillary surgery. No axillary surgery versus ALND Ten trials involving 3849 participants compared no axillary surgery versus ALND. Moderate quality evidence showed no important differences between overall survival of women in the two groups (HR 1.06, 95% confidence interval (CI) 0.96 to 1.17; 3849 participants; 10 studies) although no axillary surgery increased the risk of locoregional recurrence (HR ranging from 1.10 to 3.06; 20,863 person-years of follow-up; four studies). It was uncertain whether no surgery increased the risk of distant metastasis compared with ALND (HR 1.06, 95% CI 0.87 to 1.30; 946 participants; two studies). Low-quality evidence indicated no axillary surgery decreased the risk of lymphoedema compared with ALND (OR 0.31, 95% CI 0.23 to 0.43; 1714 participants; four studies). Axillary sampling versus ALND Six trials involving 1559 participants compared axillary sampling versus ALND. Low-quality evidence indicated similar effectiveness of axillary sampling compared with ALND in terms of overall survival (HR 0.94, 95% CI 0.73 to 1.21; 967 participants; three studies) but it was unclear whether axillary sampling led to increased risk of local recurrence compared with ALND (HR 1.41, 95% CI 0.94 to 2.12; 1404 participants; three studies). The relative effectiveness of axillary sampling and ALND for locoregional recurrence (HR 0.74, 95% CI 0.46 to 1.20; 406 participants; one study) and distant metastasis was uncertain (HR 1.05, 95% CI 0.74 to 1.49; 406 participants; one study). Lymphoedema was less likely after axillary sampling than after ALND (OR 0.32, 95% CI 0.13 to 0.81; 80 participants; one study). SLNB versus ALND Seven trials involving 9426 participants compared SLNB with ALND. Moderate-quality evidence showed similar overall survival following SLNB compared with ALND (HR 1.05, 95% CI 0.89 to 1.25; 6352 participants; three studies; moderate-quality evidence). Differences in local recurrence (HR 0.94, 95% CI 0.24 to 3.77; 516 participants; one study), locoregional recurrence (HR 0.96, 95% CI 0.74 to 1.24; 5611 participants; one study) and distant metastasis (HR 0.80, 95% CI 0.42 to 1.53; 516 participants; one study) were uncertain. However, studies showed little absolute difference in the aforementioned outcomes. Lymphoedema was less likely after SLNB than ALND (OR ranged from 0.04 to 0.60; three studies; 1965 participants; low-quality evidence). Three studies including 1755 participants reported quality of life: Investigators in two studies found quality of life better after SLNB than ALND, and in the other study observed no difference. RT versus ALND Four trials involving 2585 participants compared RT alone with ALND (with or without RT). High-quality evidence indicated that overall survival was reduced among women treated with radiotherapy alone compared with those treated with ALND (HR 1.10, 95% CI 1.00 to 1.21; 2469 participants; four studies), and local recurrence was less likely in women treated with radiotherapy than in those treated with ALND (HR 0.80, 95% CI 0.64 to 0.99; 22,256 person-years of follow-up; four studies). Risk of distant metastasis was similar for radiotherapy alone as for ALND (HR 1.07, 95% CI 0.93 to 1.25; 1313 participants; one study), and whether lymphoedema was less likely after RT alone than ALND remained uncertain (OR 0.47, 95% CI 0.16 to 1.44; 200 participants; one study). Less surgery versus ALND When combining results from all trials, treatment involving less surgery was associated with reduced overall survival compared with ALND (HR 1.08, 95% CI 1.01 to 1.17; 6478 participants; 18 studies). Whether local recurrence was reduced with less axillary surgery when compared with ALND was uncertain (HR 0.90, 95% CI 0.75 to 1.09; 24,176 participant-years of follow up; eight studies). Locoregional recurrence was more likely with less surgery than with ALND (HR 1.53, 95% CI 1.31 to 1.78; 26,880 participant-years of follow-up; seven studies). Whether risk of distant metastasis was increased after less axillary surgery compared with ALND was uncertain (HR 1.07, 95% CI 0.95 to 1.20; 2665 participants; five studies). Lymphoedema was less likely after less axillary surgery than with ALND (OR 0.37, 95% CI 0.29 to 0.46; 3964 participants; nine studies).No studies reported on disease control in the axilla.
AUTHORS' CONCLUSIONS: This review confirms the benefit of SLNB and axillary sampling as alternatives to ALND for axillary staging, supporting the view that ALND of the clinically and radiologically uninvolved axilla is no longer acceptable practice in people with breast cancer.
腋窝手术是原发性乳腺癌治疗的既定组成部分。它提供分期信息以指导辅助治疗并可能对腋窝疾病进行局部控制。有几种腋窝手术的替代方法，其中大多数旨在使一部分女性免受完全腋窝清扫术的并发症影响。
评估腋窝手术替代方法（包括完全省略此类手术）在总生存期、局部、区域和远处复发以及不良事件方面的益处和危害。
我们于2015年3月12日检索了Cochrane乳腺癌小组专业注册库、MEDLINE、Pre - MEDLINE、Embase、CENTRAL、世界卫生组织国际临床试验注册平台和ClinicalTrials.gov，无语言限制。我们还联系了研究作者并检查了参考文献列表。
随机对照试验（RCT），纳入临床定义为可手术的原发性乳腺癌女性，用于比较腋窝淋巴结清扫术（ALND）与无腋窝手术、腋窝取样或前哨淋巴结活检（SLNB）；比较腋窝取样与SLNB或无腋窝手术的RCT；比较SLNB与无腋窝手术的RCT；以及比较有或无放疗（RT）的ALND与单纯RT的RCT。
两位综述作者独立评估每项可能相关的试验是否纳入。我们独立从所有纳入试验中提取结局数据、偏倚风险信息和研究特征。我们根据试验干预措施汇总数据，对于事件发生时间结局使用风险比（HRs），对于二元结局使用比值比（OR）。
本综述纳入了26项RCT。研究的选择偏倚风险低或不明确。未进行盲法，但这仅被视为测量可能具有主观性的结局的偏倚来源。我们未找到比较腋窝取样与SLNB、腋窝取样与无腋窝手术或SLNB与无腋窝手术的RCT。无腋窝手术与ALND 10项试验涉及3849名参与者，比较了无腋窝手术与ALND。中等质量证据表明，两组女性的总生存期无重要差异（HR 1.06，95%置信区间（CI）0.96至1.17；3849名参与者；10项研究），尽管无腋窝手术增加了局部区域复发的风险（HR范围为1.10至3.06；20863人年的随访；4项研究）。与ALND相比，无手术是否增加远处转移风险尚不确定（HR 1.06，95% CI 0.87至1.30；946名参与者；2项研究）。低质量证据表明，与ALND相比，无腋窝手术降低了淋巴水肿的风险（OR 0.31，95% CI 0.23至0.43；1714名参与者；4项研究）。腋窝取样与ALND 6项试验涉及1559名参与者，比较了腋窝取样与ALND。低质量证据表明，腋窝取样与ALND在总生存期方面效果相似（HR 0.94，95% CI 0.73至1.21；967名参与者；3项研究），但与ALND相比，腋窝取样是否会增加局部复发风险尚不清楚（HR 1.41，95% CI 0.94至2.12；1404名参与者；3项研究）。腋窝取样和ALND在局部区域复发（HR 0.74，95% CI 0.46至1.20；406名参与者；1项研究）和远处转移方面的相对有效性尚不确定（HR 1.05，95% CI 0.74至1.49；406名参与者；1项研究）。腋窝取样后发生淋巴水肿的可能性低于ALND（OR 0.32，95% CI 0.13至0.81；80名参与者；1项研究）。SLNB与ALND 7项试验涉及9426名参与者，比较了SLNB与ALND。中等质量证据表明，与ALND相比，SLNB后的总生存期相似（HR 1.05，95% CI 0.89至1.25；6352名参与者；3项研究；中等质量证据）。局部复发（HR 0.94，95% CI 0.24至3.77；516名参与者；1项研究）、局部区域复发（HR 0.96，95% CI 0.74至1.24；5611名参与者；1项研究）和远处转移（HR 0.80，95% CI 0.42至1.53；516名参与者；1项研究）的差异尚不确定。然而，研究表明上述结局的绝对差异很小。SLNB后发生淋巴水肿的可能性低于ALND（OR范围为0.04至0.60；3项研究；1965名参与者；低质量证据）。3项研究包括1755名参与者报告了生活质量：两项研究的研究者发现SLNB后的生活质量优于ALND，另一项研究未观察到差异。RT与ALND 4项试验涉及2585名参与者，比较了单纯RT与ALND（有或无RT）。高质量证据表明，与接受ALND治疗的女性相比，单纯接受放疗的女性总生存期降低（HR 1.10，95% CI 1.
