Major Finding: Overall 5-year survival was 91.8% with axillary node dissection and 92.5% without it; the 5-year disease-free survival was 82.2% with axillary node dissection and 83.9% without it. The differences were not significant.
Data Source: A phase III noninferiority trial involving 891 women with invasive node-positive breast cancer treated at 115 medical centers.
Disclosures: This study was supported by the National Cancer Institute. No financial conflicts of interest were reported.
Axillary lymph node dissection did not improve overall survival or disease-free survival in women with T1-T2 breast cancer who were found to have limited metastasis on sentinel node dissection.
In the American College of Surgeons Oncology Group's Z0011 trial, survival was nearly identical between women who underwent lumpectomy and sentinel node dissection alone, followed by adjuvant chemotherapy and tangential-field whole-breast irradiation, and women who underwent axillary node dissection when sentinel node biopsy revealed limited metastasis, followed by the same chemotherapy and irradiation.
“The findings from Z0011 document the high rate of locoregional control achieved with modern multimodal therapy, even without axillary lymph node dissection,” said Dr. Armando E. Giuliano of John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, Calif., and his associates.
The results also imply that axillary node dissection is no longer warranted in such patients, because “the only additional information gained … is the number of nodes containing metastases. This prognostic information is unlikely to change systemic therapy decisions and is obtained at the cost of a significant increase in morbidity,” the investigators noted.
Forgoing the standard practice of axillary node dissection when sentinel nodes reveal metastasis constitutes a practice change that “would improve clinical outcomes in thousands of women each year by reducing the complications associated with axillary lymph node dissection and improving quality of life with no diminution in survival,” they concluded.
The need for axillary node dissection when sentinel nodes are found to have metastasis has been called into question for years, and use of this “standard” practice has declined. Until now, “no study has conclusively demonstrated a survival benefit or detriment for omitting axillary node dissection,” they said.
The ACS Oncology Group's Z0011 trial, begun in the late 1990s, was intended to definitively answer that question. The phase III “noninferiority” trial involved 891 women who were followed at 115 centers after undergoing lumpectomy and sentinel node dissection revealing metastasis. These subjects were randomly assigned to undergo standard axillary node dissection (445 patients) or no axillary node dissection (446 patients), followed by whole-breast tangential-field radiation (not third-field nodal irradiation) and whatever adjuvant systemic therapy their treating physicians deemed necessary.
The trial's enrollment was halted early in 2004 “because of concerns regarding the extremely low mortality rate.” It was determined that accrual of more patients would not alter the survival findings, and final follow-up for the analysis was completed in 2010.
After a median of 6 years of follow-up, there were 94 deaths. The 5-year overall survival was 92.5% with sentinel node dissection alone and 91.8% with full axillary node dissection, a nonsignificant difference. The 5-year disease-free survival rate was 83.9% with sentinel node dissection alone and 82.2% with full axillary node dissection, also a nonsignificant difference. These results were consistent across several subgroups of patients, regardless of patient age, tumor size, tumor hormone-receptor status, or which adjuvant therapies were received.
The two study groups did differ significantly in morbidities related to lymph node dissection. The rate of wound infection, axillary seromas, and paresthesias was markedly higher for women who underwent axillary node dissection (70%) than for those who did not (25%). Lymphedema also was more common with axillary node dissection.
“The excellent local and distant outcomes in this study highlight the effects of multiple changes in breast cancer management” in recent years, including “improved imaging, more detailed pathological evaluation, improved planning of surgical and radiation approaches, and more effective systemic therapy,” Dr. Giuliano and his colleagues said (JAMA 2011;305:569-75). They emphasized that this trial did not include patients who had mastectomy, lumpectomy without radiation therapy, partial-breast irradiation, or whole-breast irradiation in the prone position (which would not treat the low axilla). In such patients, “axillary lymph node dissection remains standard practice when sentinel lymph node dissection identifies a positive sentinel lymph node.”
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A Definitive Answer
The American College of Surgeons Oncology Group Z0011 trial “definitively showed that axillary lymph node dissection is not beneficial,” said Dr. Grant Walter Carlson and Dr. William C. Wood.
Even though 27% of the women who underwent axillary node biopsy were found to have additional lymph nodes containing metastases, the axillary recurrence rates were similar between the two groups.