Sentinel lymph node biopsy using dye alone in patients with initially cN1 breast cancer and ycN0 status after neoadjuvant therapy: a multicenter diagnostic trial

<h2>Abstract</h2><h3>Background</h3> Given the known complications associated with axillary lymph node dissection (ALND) and the limited application of radiolabeled colloid tracking in China, dye-only sentinel lymph node biopsy (SLNB) is proposed as a feasible and alternative surgical treatment strategy for patients with initially clinically node-positive (cN1) breast cancer to a clinically node-negative (ycN0) status after neoadjuvant therapy (NAT). However, the clinical diagnostic performance of dye-only SLNB needs further verification. <h3>Methods</h3> We conducted a multicenter diagnostic clinical trial from July 2019 to September 2023 by recruiting 230 patients from 12 participating centers across six provinces in China. Adult women with clinical stage T1-4N1M0 breast cancer and ycN0 status after NAT were eligible. SLNB and ALND were performed sequentially for patients, while a single dye was used to guide sentinel lymph nodes during the operation. The primary endpoint was the false-negative rate (FNR) of SLNB after NAT in women with ycN0 disease. Furthermore, subgroup analyses were conducted by age, body mass index (BMI), the number of SLNs removed and tumor subtype. The trial is registered on www.chictr.org.cn (identifier: ChiCTR1900026929) and www.isrctn.com (identifier: ISRCTN31364289). <h3>Findings</h3> The detection rate of single-dye was 95.22% (219/230). Pathological examinations showed positive lymph node findings in 117 of 230 patients. SLNB was successful in 212 out of the 219 patients (96.80%). The FNR of dye-alone SLNB was 5.98% (7/117; 95% CI, 2.44%-11.94%). Furthermore, the FNR was lower in women under 60 years of age (2.33% vs. 16.13% older than 60 years, <i>P</i>=0.0139), with body mass index under 25 kg/m² (2.60% vs. 12.5%, <i>P</i>=0.0452), and with four or more SLNs (2.53% vs. 13.16% with fewer than four SLNs, <i>P</i>=0.0358). For HR negative/HER-2 positive cases, the FNR was 0%. <h3>Interpretation</h3> SLNB with dye alone in patients with initially cN1 breast cancer and ycN0 after neoadjuvant therapy resulted in clinically acceptable rate of FNR. When four or more SLNs are detected, patients with age ≤ 60 years, BMI<25km/m² and Her2-positive would derive additional benefit from dye-alone SLNB. <h3>Funding</h3> This trial was funded by Tackling Key Problems and Serving Local Projects of Liaoning Province (ZF20190006, to BC), National Natural Science Foundation of China (82073282 and 82203873, to AZ) and Joint Fund Project of the Science and Technology Program of Liaoning Province (2023012141-JH3/4600, to AZ).