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 (cN0) breast cancer. The American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) trial examined the false-negative rate of sentinel node surgery for staging the axilla after neoadjuvant chemotherapy in women who presented 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 nodes examined—slightly higher than the 10% rate expected with sentinel lymph node surgery in women with cN0 disease.¹

Study Details

The trial enrolled 756 women who had clinical T0-4, N1-2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both sentinel node surgery and axillary node dissection. Sentinel node surgery using both blue dye and a radiolabeled colloid mapping agent was encouraged.

The primary endpoint was the false-negative rate of sentinel 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 nodes examined would be greater than the 10% rate expected with sentinel 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 node surgery, 4% had mapping with blue dye only, 17% with radiolabeled colloid only, and 79% with both radiolabeled colloid and blue dye, as recommended by the protocol.

False-Negative Rate of 12.6%

Of the 663 patients, 649 underwent chemotherapy followed by both sentinel node surgery and axillary node dissection.

A sentinel lymph node could not be identified in 46 patients (7.1%), and only one sentinel node was removed in 78 patients (12.0%). Of the remaining 525 patients with two or more sentinel 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 nodes in 108 (20.6%), confined to nodes removed with axillary node dissection in 39 (7.4%), and present in nodes from both procedures in 163 (31.1%). Thus, sentinel 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 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 at least three sentinel nodes (P = .007, false-negative rate = 9.1% for ≥ 3 sentinel nodes vs 21.1% for 2). Multivariate analysis showed that after accounting for the number of sentinel nodes examined (2 vs ≥ 3), 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 nodes excised followed by axillary 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 nodes in six patients and in both sentinel nodes and nodes excised on axillary node dissection in eight 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 2 [sentinel lymph nodes] were associated with a lower likelihood of false-negative [sentinel node] findings. Among women with cN1 breast cancer who received neoadjuvant chemotherapy and had 2 or more [sentinel nodes] examined, the false-negative rate was 12.6% … with [sentinel 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 node] surgery as an alternative to [axillary node dissection] in this patient population. ■

Disclosure: The study was supported by a grant from the National Cancer Institute awarded to ACOSOG. For full disclosures of the study authors, visit jama.jamanetwork.com.

Reference

1. Boughey JC, Suman VJ, Mittendorf EA, et al: Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: The ACOSOG Z1071 (Alliance) clinical trial. JAMA 310:1455-1461, 2013.