JAMA 2011-02-09
Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.
ABSTRACT
CONTEXT
Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival.
OBJECTIVE
To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.
DESIGN, SETTING, AND PATIENTS
The American College of Surgeons Oncology Group Z0011 trial, a phase 3 noninferiority trial conducted at 115 sites and enrolling patients from May 1999 to December 2004. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and 1 to 2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin-eosin staining on permanent section. Targeted enrollment was 1900 women with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected.
INTERVENTIONS
All patients underwent lumpectomy and tangential whole-breast irradiation. Those with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Systemic therapy was at the discretion of the treating physician.
MAIN OUTCOME MEASURES
Overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND. Disease-free survival was a secondary end point.
RESULTS
Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up, March 4, 2010), 5-year overall survival was 91.8% (95% confidence interval [CI], 89.1%-94.5%) with ALND and 92.5% (95% CI, 90.0%-95.1%) with SLND alone; 5-year disease-free survival was 82.2% (95% CI, 78.3%-86.3%) with ALND and 83.9% (95% CI, 80.2%-87.9%) with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 (90% CI, 0.56-1.11) without adjustment and 0.87 (90% CI, 0.62-1.23) after adjusting for age and adjuvant therapy.
CONCLUSION
Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00003855.
Related Questions
After the publication of ACOSOG Z11 we are seeing these patients in increasing numbers.
New answer by Radiation Oncologist at University of Maryland Shore Medical Center at Easton (March 20, 2018)
Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS):a randomised, multicentre, open-label, phase 3non-inferiority ...
In particular, I have a patient who underwent lumpectomy for a T3 tumor with positive margins and 1/2 SLN+. She is now scheduled for mastectomy ...
New comment by Radiation Oncologist at Cleveland Clinic ( February 3, 2021)
I don't use high tangents commonly outside of ER+ N1mic cases. Otherwise, I tend to add SC field to whole breast fields in such cases and treat breast and nodes 40/15.
Did the EBCTCG meta-analysis change your practice?
New comment by Radiation Oncologist at UNC School of Medicine ( August 2, 2023)
These are very challenging questions. The randomized data demonstrated an improvement in overall survival treated comprehensively (chest wall and nodes). So, it seems prudent ...
If no, in what patients should axillary ultrasounds be performed?
New answer by Radiation Oncologist at Varian Medical Systems/Allegheny health network (December 21, 2016)
The practice has changed a bit with Z11 and AMAROS. For all invasive cancer we do perform sonogram but ifthe nodes are not palpable but only suspicious on ultrasound we don't ...
New comment by at Duke University Medical Center ( January 27, 2021)
Since a radiographically negative axilla was not an inclusion criteria for either study, it is not known how many patients were excluded because of sonographically detected ly...
Does it make sense to resect only the axillary nodes, but not the other involved nodal regions? Regional nodal radiation will be given.
New answer by Radiation Oncologist at Penn Medicine (June 21, 2018)
This is a great question that I have seen many times clinically. The point is often made that Z-11 did not include such patients and therefore the logic to omit ALND with limi...
e.g. Gingras et al., JNCI 2017, a secondary analysis of the ALTTO trial?
New answer by Radiation Oncologist at Cleveland Clinic (September 13, 2020)
When I evaluate patients in this situation, BCS + SLN with positive node, I tend to think about the decision as to the whole breast RT+/- RNI and use AMAROS/Z011 to frame my d...
Comprehensice RNI? High tangents? Whole breast only? Does ER/PR/Her2 status influence your decision?
New comment by Radiation Oncologist at TSPMG/Kaiser Permanente ( March 2, 2021)
@Jacob E. Locke, although the Z0011 protocol required that patients receive whole-breast RT using standard tangential fields and specified that a third field of directed nodal...
How would this affect adjuvant radiation plan in breast conservation therapy patients and mastectomy patients?
New comment by Medical Oncologist at Banner MD Anderson Cancer Center ( August 30, 2021)
In RxPonder study, only 61% of patients had node dissection. 39% of patients only had SLN resection. The HR for iDFS events was 0.82 favoring the chemotherapy arm, but this wa...
New comment by Radiation Oncologist at Stroger Hospital ( December 18, 2022)
Interesting analysis.