Does Axillary Node Dissection Boost Survival?

Lidia Schapira, MD


February 24, 2011

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

Giuliano AE, Hunt K, Ballman K, et al
JAMA. 2011;305:569-575

Study Summary

In the late 1990s, the American College of Surgeons Oncology Group designed and began the multicenter Z0011 trial. The primary aim was to determine the effects of axillary lymph node dissections (ALND) on overall survival in women with invasive breast cancer who had sentinel lymph node (SLN) metastases treated with lumpectomy, adjuvant systemic therapy, and tangential field radiation therapy.

Giuliano and colleagues have reported the results of their multicenter, randomized phase 3 clinical trial. They enrolled women with histologically confirmed invasive cancer that clinically measured 5 cm or less, was not associated with palpable adenopathy, and had SLNs containing metastatic breast cancer documented by frozen section, touch prep, or hematoxylin and eosin on permanent section. Primary surgical treatment was with lumpectomy to clear margins, defined as no tumor on ink. Women were ineligible if they had 3 or more positive SLNs, matted nodes, or gross nodal disease. Women were randomly assigned after SLND and stratified according to age (≥ 50 years or < 50 years), estrogen receptor status, and tumor size. Eligible women were randomly assigned to ALND or control group and no further axillary-specific intervention was allowed; specifically, no third field nodal irradiation.

The primary endpoint was overall survival. A short-term primary endpoint was occurrence of surgical morbidities. A secondary endpoint was disease-free survival. The first patient was enrolled in 1999 and accrual closed in December of 2004 because of concerns about an extremely low mortality rate. The initial targeted accrual was 1900 and instead the trial accrued only 891. Patients were enrolled from 115 institutions.

Adjuvant systemic therapy was delivered to 96% of women in the ALND group and 97% in the SLND-only group. The number of women who received chemotherapy vs endocrine therapy did not differ. The same number of women in each group received whole breast irradiation (89%).

At a median follow-up of 6.3 years, there were 94 deaths (SLND 42, ALND 52); thus the use of SLND alone did not result in inferior survival. The 5-year survival rates were 92.5 % for the SLND group and 91.8% in the ALND group. This was substantially higher than anticipated at the time of trial design. Disease-free survival did not differ significantly between groups. The 5-year disease-free survival was 83.9% for the SLND-alone group and 82.2% for the ALND group. The 5-year rates of locoregional relapse were 1.6% for the SLND-alone group and 3.1% for the ALND group. Locoregional recurrence-free survival was similar and exceeded 95% for both groups.

The investigators had previously reported on the excess of wound infections, axillary seromas, and paresthesias among the patients in the Z0011 trial assigned to the ALND group. They concluded that the use of SLND alone in patients with limited sentinel node involvement who also received radiation and systemic therapy did not result in inferior survival.


The results of this study constitute good news for patients with early stage breast cancer and disease limited to 1-2 sentinel nodes. The study took years to complete and closed early as a result of the small number of "events." This is also good news and reflects the success of contemporary radiation therapy and improved systemic therapy. In fact, the participants in this study have very low risk for local failure or distant relapse. The fact that only 1% of patients had axillary nodal recurrences likely reflects careful preoperative staging and more detailed pathologic evaluation as well as improved systemic therapy and modern radiation planning and schedules.

Giuliano and colleagues point out that it is very unlikely that survival differences will emerge after longer follow-up. Certainly, axillary recurrence is typically an early event. The limitations of the study were the stated failure to achieve target accrual and a randomization imbalance that favored the SLND group. It is important to bear in mind that these results do not apply to patients undergoing mastectomy, those undergoing lumpectomy without radiation, those receiving partial breast irradiation or neoadjuvant therapy, or those who receive radiation that does not cover the axilla.

This study received considerable attention in the media and lay press, and I anticipate that patients will not only welcome the news, but also help drive change to avoid an additional surgical procedure which, for some, appears unnecessary.



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