ACOSOG Z1071 Trial Does Not Support Sentinel Lymph Node Surgery Following Neoadjuvant Chemotherapy for Node-Positive cN1 Breast Cancer
Sentinel lymph node surgery provides reliable nodal staging information and is associated with less morbidity than axillary lymph node dissection in patients with clinically node-negative breast cancer. The American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) trial examined the false-negative rate of sentinel lymph node surgery for staging the axilla after neoadjuvant chemotherapy in women with node-positive cN1 breast cancer. As reported in the Journal of the American Medical Association by Judy C. Boughey, MD, of the Mayo Clinic, and colleagues, the false-negative rate was found to be 12.6% in women with two or more sentinel lymph nodes examined, higher than the 10% rate expected with sentinel lymph node surgery in women with clinically node-negative disease. The investigators recommended that improvements in the strategy be made before it can be used as an alternative to axillary lymph node dissection in women with cN1 disease.
Study Details
The trial enrolled 756 women who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Patients underwent both sentinel lymph node surgery and axillary lymph node dissection following chemotherapy. Sentinel lymph node surgery using both blue dye and a radiolabeled colloid mapping agent was encouraged. The primary endpoint was the false-negative rate of sentinel lymph node surgery after chemotherapy in women who presented with cN1 disease, with the study evaluating the likelihood that the rate in patients with two or more sentinel lymph nodes examined would be greater than the 10% rate expected with sentinel lymph node surgery in women who present with cN0 disease.
Of 663 evaluable patients with cN1 disease, 30% had HER2-positive disease, 45% had hormone receptor–positive/HER2-negative disease, and 23.5% had triple-negative disease. Most had clinical T2 disease (56%), invasive ductal carcinoma (89%), core needle axillary biopsy (61%), anthracycline plus taxane chemotherapy (75%), and no palpable axillary adenopathy after chemotherapy (84%). In total, 92% completed neoadjuvant chemotherapy. Of 651 patients with cN1 disease undergoing sentinel lymph node surgery, 4% had mapping with blue dye only, 17% with radiolabeled colloid only, and 79% with both.
False-Negative Rate of 12.6%
Of the 663 patients, 649 underwent chemotherapy followed by both sentinel lymph node surgery and axillary lymph node dissection.
A sentinel lymph node could not be identified in 46 patients (7.1%), and only one sentinel lymph node was removed in 78 patients (12.0%). Of the remaining 525 patients with two or more sentinel lymph nodes removed, no cancer was identified in the axillary nodes of 215 patients, yielding a pathologic complete nodal response of 41.0% (95% confidence interval [CI] = 36.7%–45.3%). In the remaining 310 patients, residual nodal disease was confined to sentinel lymph nodes in 108 (20.6%), confined to nodes removed with axillary lymph node dissection in 39 (7.4%), and present in nodes from both procedures in 163 (31.1%). Thus, sentinel lymph node findings were false-negative in 39 of the 310 patients with residual nodal disease, yielding a false-negative rate of 12.6% (90% Bayesian credible interval = 9.85%–16.05%).
Reduced Likelihood of False-Negatives
A bivariable analysis showed that the likelihood of false-negative sentinel lymph node findings was significantly reduced when mapping was performed with the combination of blue dye and radiolabeled colloid (P = .05, false-negative rate 10.8% with combination vs 20.3% with single agent) and by examination of three or more sentinel lymph nodes (P = .007, false-negative rate of 9.1% for three or more sentinel lymph nodes vs 21.1% for two). Multivariate analysis showed that after accounting for number of sentinel lymph nodes examined (two vs three or more), no other factors were significant in explaining variability in the likelihood of a false-negative finding.
The trial included 26 women with cN2 disease with at least two sentinel lymph nodes excised followed by axillary lymph node dissection. Among these, 12 had no residual nodal disease, yielding a pathologic complete nodal response rate of 46.1% (95% CI = 26.6%–66.6%). Among the remaining 14, residual nodal disease was found only in sentinel lymph nodes in 6 patients and in both sentinel lymph nodes and nodes excised on axillary lymph node dissection in 8 patients, yielding a false-negative rate of 0% (95% CI = 0%–23.2%).
The investigators concluded: “[O]ur trial found that both the use of dual-agent mapping and recovery of more than [two sentinel lymph nodes] were associated with a lower likelihood of false-negative [sentinel lymph node] findings. Among women with cN1 breast cancer who received neoadjuvant chemotherapy and had [two or more sentinel lymph nodes] examined, the false-negative rate was 12.6% ... with [sentinel lymph node] surgery and exceeded the prespecified threshold of 10%. Given this acceptability threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of [sentinel lymph node] surgery as an alternative to [axillary lymph node dissection] in this patient population.”
The study was supported by a grant from the National Cancer Institute awarded to ACOSOG.
Kelly K. Hunt, MD, of The University of Texas MD Anderson Cancer Center in Houston, is the corresponding author for the Journal of the American Medical Association article.
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