Dissection in Breast Cancer with Sentinel-Node Metastasis

Posted by Carla Rothaus, MD

Published April 3, 2024

In this trial, how did sentinel-node biopsy only compare with completion axillary-lymph-node dissection regarding 5-year recurrence-free survival?

A recent publication by de Boniface et al. reported the results of the prespecified secondary end point of recurrence-free survival in an ongoing phase 3 noninferiority trial in which patients with clinically node-negative breast cancer with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Read the NEJM Original Article here.

Clinical Pearls

Q: When did the use of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and one or two sentinel-lymph-node metastases begin to decline?

A: In 2010 and 2011, the American College of Surgeons Oncology Group Z0011 trial showed the safety of the omission of completion axillary-lymph-node dissection (the removal of additional axillary lymph nodes after biopsy of sentinel lymph nodes has revealed metastases) among patients with clinically node-negative (cN0) breast cancer undergoing breast-conserving surgery and whole-breast radiotherapy in whom sentinel-lymph-node biopsy had revealed one or two metastases. Since then, the use of completion axillary-lymph-node dissection has been steadily decreasing.

Q: What was the aim of the trial by de Boniface et al.?

A: The aim of this trial was to validate results from previous trials in a sufficiently large cohort focused only on patients with sentinel-node macrometastases and to extend eligibility criteria to include important underrepresented subgroups — namely, patients undergoing mastectomy, those with sentinel-node extracapsular extension or T3 tumors (tumor size, >50 mm in the largest dimension), and men. The primary end point was overall survival. The authors currently report the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival.

Morning Report Questions

Q: In this trial, how did sentinel-node biopsy only compare with completion axillary- lymph-node dissection regarding 5-year recurrence-free survival?

A: The calculation of the estimated 5-year recurrence-free survival was based on 180 patients (7.1%) who had an event within 5 years after randomization: 89 patients (6.7%) in the sentinel-node biopsy–only group and 91 (7.6%) in the dissection group. The estimated 5-year recurrence-free survival was 89.7% (95% CI, 87.5 to 91.9) in the sentinel-node biopsy–only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group. After adjustment for the stratification factor of country, the hazard ratio for recurrence or death in the sentinel-node biopsy–only group as compared with the dissection group was 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the noninferiority margin. The result in the modified intention-to-treat population (hazard ratio, 0.89; 95% CI, 0.67 to 1.19) was similar to that in the per-protocol population.

Q: What were the results of analyses of recurrence-free survival in subgroups that had been previously underrepresented?

A: Subgroup analyses were performed in clinically relevant subgroups. Too few male patients (10 [0.4%]) had been enrolled for subgroup analysis to be possible. Female and male adult patients who had cN0 breast cancer with a tumor stage of T1, T2, or T3 and one or two sentinel-node macrometastases were eligible for inclusion. More than one third of the patients underwent mastectomy. Approximately one third of the patients had extracapsular extension in the sentinel-node biopsy sample. The hazard ratio for recurrence or death in the sentinel-node biopsy–only group as compared with the dissection group included 1.00 in all the subgroups except in the subgroup of patients with estrogen-receptor–positive, human epidermal growth factor receptor 2-positive disease, in which sentinel-node biopsy only appeared to be better.