Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis A Randomized Clinical Trial

John Wayne Cancer Institute at Saint John's Health Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 02/2011; 305(6):569-75. DOI: 10.1001/jama.2011.90
Source: PubMed


Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival.
To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.
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.
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.
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.
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.
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. Identifier: NCT00003855.

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    • "The Z-0011 trial has advocated that ALND is not necessary if < 3 nodes are involved (Giuliano et al. 2010). Giuliano et al. (2011) summarized total nodal involvement in ALND and SLND alone groups, 21.0% of patients undergoing ALND had 3 or more involved nodes compared with 3.7% undergoing SLND alone (Giuliano et al. 2011). Completion ALND quantifies total nodal burden, defines prognosis and can determine adjuvant treatments in addition to maximising local disease control (Kothari et al. 2012). "
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    • "The choice between the two methods of intraoperative analysis was dictated by the timing of introduction of the OSNA device, which today represents the method of choice in the centres participating in the trial. A decision about axillary management was made intraoperatively, taking into account the results of recent studies (Giuliano et al. 2011; Galimberti et al. 2013). End points The primary endpoint was the DR per patient with either SPIO or 99m Tc. "
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    • "Studies have shown that axillary lymph node dissection may not affect the survival of breast cancer patients who receive breast-conserving therapy and have negative or 1-2 positive sentinel lymph nodes, on the basis of which investigators have proposed that axillary lymph node dissection should not be performed [1] [2]. "
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