A multicenter randomized phase III trial of 5,611 patients randomly assigned to either SLN plus ALND or to SLN resection alone with ALND only if the SLNs were positive showed no detectable difference in OS, disease-free survival (DFS), and regional control. OS was 91.8% versus 90.3% in the SLN plus ALND and SLN alone, respectively (P = .12).[Level of evidence: 1iiA]
Similarly, a single-center randomized trial of 532 patients with T1 carcinomas undergoing either SLN biopsy plus complete axillary dissection or SLN biopsy alone showed, after a median follow-up of 78 months, no difference in 5-year DFS (92.9% in the SLN biopsy without routine axillary dissection group vs. 88.9% in patients having axillary dissection irrespective of SLN findings, P = .1).[Level of evidence: 1iiDii]
The reported false-negative rates of SLN biopsy using axillary node dissection as the gold standard range from 0% to 15% with an average of 8.8%. The success rate varies with the surgeon's experience and with the primary tumor characteristics. In general, studies have restricted the use of SLN biopsy to women with T1 and T2 disease, without evidence of multifocal involvement or clinically positive lymph nodes. SLN biopsy alone is associated with less morbidity than axillary lymphadenectomy. In a randomized trial of 1,031 women that compared SLN biopsy followed by axillary dissection when the SLN was positive with axillary dissection in all patients, quality of life at 1 year (as assessed by the frequency of patients experiencing a clinically significant deterioration in the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Breast scale) was superior in the SLN biopsy group (23% vs. 35% deteriorating in the SLN biopsy vs. axillary dissection groups, respectively; P = .001).[Level of evidence 1iiC] Arm function was also better in the SLN group. The NSABP-B-32 (NCT00003830) trial, a randomized study of 5,611 women, found the same results with respect to accuracy and technical success. Based on this body of evidence, SLN biopsy is the standard initial surgical staging procedure of the axilla for women with invasive breast cancer.
A multicenter, randomized clinical trial sought to determine whether ALND is required after an SLN biopsy reveals an SLN metastasis of breast cancer. This phase III noninferiority trial planned to randomly assign 1,900 women with clinical T1–T2 invasive breast cancer without palpable adenopathy and with one to two SLNs containing metastases identified by frozen section to undergo ALND versus no further axillary treatment. All patients underwent lumpectomy, tangential whole-breast irradiation, and appropriate systemic therapy, and OS was the primary endpoint. Because of enrollment challenges, a total of 891 women out of a target enrollment of 1,900 women were randomly assigned to one of the two treatment arms. At a median follow-up of 6.3 years, 5-year OS was 91.8% (95% CI, 89.1%–94.5%) with ALND and 92.5% (95% CI, 90.0–95.1%) with SLN biopsy alone. The secondary endpoint of 5-year disease-free survival (DFS) was 82.2% (95% CI, 78.3%–86.3%) with ALND and 83.9% (95% CI, 80.2%–87.9%) with SLN biopsy alone.[Level of evidence: 1iiA] On the basis of the results of this trial, the medical necessity of ALND after a positive SLN biopsy in patients with limited SLN-positive breast cancer treated with breast conservation, radiation, and systemic therapy is called into question.