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
Would you pursue ALND in a patient with breast cancer who had a negative sentinel node biopsy but had a non-sentinel node that was positive?
If the patient had a clinically negative axilla and otherwise meets criteria for Z0011, I would probably omit completion ALND in the setting of an incidentally identified non-sentinel node at the time of sentinel node biopsy. We know that the sentinel node biopsy carries a false negative rate of app...
What evidence supports the use of high tangents for pN1mic breast cancer?
This is a great question. To add to the excellent answers from @Dr. First Last and @Dr. First Last, here are some of my thoughts on this topic:At the time of MA.20, the size of nodal metastasis was not routinely measured so it is unclear what percent of patients in MA.20, if any, had micrometastases...
Do you recommend axillary dissection for women with ER+ breast cancer and low risk Oncotype or Mammaprint if single node positive with only 1-2 SLN removed, to ensure <4 nodes positive?
No, I see no need to do dissection in this setting. Unless there is clinical or imaging evidence of gross disease, radiation should adequately control microscopic residual disease in the axilla.
What is the current criteria for sentinel node biopsy over a full axillary lymph node dissection in a patient with breast cancer?
This is a rapidly evolving space.For patients that cN0 with 1-2 or 3 SLN+, ALND can be omitted without gross ECE. Also, the NCCN guidelines have allowed for a similar approach with patients with 2 or fewer nodes on imaging/biopsy. While most patients on AMAROS/Z011 had breast conservation, this appr...
For a postmenopausal patient with a pT2N0 breast cancer s/p BCS+SNB who qualifies for MA20, how do you decide between RNI, high tangents, and standard whole breast RT?
TL;DR: "This patient would have fit Z11 criteria - if they had positive nodes. Patients did very well with tangents/high tangents. For N0 patients that would have been otherwise eligible for Z11, I would treat with standard whole breast RT." The absolute reduction in isolated LRR in MA.20 was 5% at ...
For postmastectomy patients who have >2 sentinel nodes involved, would you recommend a completion axillary dissection or proceed with PMRT?
This is a question that is still debated. I am comfortable extrapolating AMAROS/Z011 to mastectomy patients despite the limited number of patients undergoing mastectomy in AMAROS.In patients with 2-3 SLN involved (that were cN0), I would be ok with PMRT and omitting ALND as long as no ECE. If > 3 LN...
Would you treat a male breast cancer patient with post-mastectomy radiotherapy for a single positive sentinel lymph node and a low Oncotype?
In the setting of a mastectomy with a positive SLN and no ALND, I tend to extrapolate from AMAROS. While Z0011 had no mastectomy and AMAROS limited mastectomy patients, I am comfortable extrapolating axillary management to mastectomy setting.In this case, I would offer PMRT to chest wall and regiona...
In light of RxPonder results for postmenopausal women with early stage node positive HR+HER2- breast cancer, when is there a role for full axillary LN dissection to confirm degree of nodal involvement and when would sentinel LN evaluation be sufficient?
I don’t think the RxPonder study changes surgical management. Still follow Z0011 paradigm.
What group of patients is suitable for breast radiation using high tangents?
I could consider high tangents for patients with ER+ disease and N1mic. If patients have ER- and N1mic or N1 disease with macromets, I tend to add RNI.
Would you give/omit regional nodal irradiation in low nodal burden ER- Her2+ disease s/p BCS with SLNB?
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 decision making.In an ER-negative patient, I would favor RNI, extrapolating from MA20 (where patients had an ALND, and 85% 1-3...
Would you recommend axillary dissection for a patient with a clinically positive SCV or IMN node, who has a clinical CR to neoadjuvant chemo, but a positive SLNB?
My approach for this is to treat comprehensively with RT and boost any visible node/location where the prechemotherapy node existed and was not removed at surgery.
What treatment fields do you use for N1mi breast cancer after lumpectomy/SLNB?
We treat with modified tangents including level 1 and 2 nodes in tangential beam for micrometastases. ER, PR, and her2 neu or oncotype does influence the decision for micrometastases after lumpectomy.
Should axillary imaging be routinely performed in all patients with a new diagnosis of breast cancer?
This issue has been debated but I would argue that patients with a new diagnosis of breast cancer should not undergo routine screening US of the axilla to look for clinically occult disease. The axillary US should be limited to diagnostic imaging for clinically suspicious nodes on clinical exam or b...
Do you routinely perform an axillary ultrasound in women with newly diagnosed breast cancer without palpable axillary nodes?
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 routinely perform a percutaneus bx. The idea is these patients are still suitable for SLNB and were included in Z11. SLNB wou...
In light of the AMAROS trial, how do you decide between ALND vs. axillary RT?
These clinical scenarios will be faced more often by radiation oncologists.In the old French and NSABP B4 data, the regional control rates between surgery and radiation were very similar for clinically node negative patients, but these studies did not gain much traction because chemotherapy decision...
Is PMRT considered the standard of care in women with 1-3 positive axillary lymph nodes?
I come to this question with a somewhat different stance than we have traditionally thought. To me, the following things seem clear:1) In our modern randomized trials of PMRT (British Columbia and Danish 82b and c) there was no difference in the OS advantage of RT based on # of positive nodes (1-3 v...
How do you treat women who have breast-conserving surgery with positive sentinel node/s and no axillary dissection?
Three separate points to make: 1. Z-11 is often misquoted. The Z-11 trial did not randomize patients to plus or minus nodal radiation. That question was asked in the MA 20 study. In the MA 20 study, as well as a few other studies, the addition of regional radiation provides a meaningful impact on ou...