Background: This study measures the feasibility and accuracy of sentinel lymph node biopsy (SLNB) with triple-tracers (TT-SLNB) which combines carbon nanoparticles (CNS) with dual tracers of radioisotope and blue dye, hoping to achieve an optimized method of SLNB after neoadjuvant chemotherapy (NAC) in ycN0 breast cancer patients with pretreatment positive axillary lymph nodes. Methods: Clinically node-negative invasive breast cancer patients with pre-NAC positive axillary lymph nodes who received surgeries from November 2020 to January 2021 were included. CNS was injected at the peritumoral site the day before surgery. Standard dual-tracer (SD)-SLNs were defined as blue-colored and/or hot nodes, and TT-SLNs were defined as lymph nodes detected by any of hot, blue-stained, black-stained, and/or palpated SLNs. All patients received subsequent axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were calculated. Results: Seventy-six of 121 (62.8%) breast cancer patients converted to cN0 after NAC and received TT-SLNB. After NAC, 28.95% (22/76) achieved overall (breast and axilla) pCR. The DR was 94.74% (72/76), 88.16% (67/76) and 96.05% (73/76) for SLNB with single-tracer of CNS (CNS-SLNB), SD-SLNB, and TT-SLNB, respectively. The FNR was 22.86% (8/35) for CNS-SLNB and 10% (3/30) for SD-SLNB. The FNR of TT-SLNB was 5.71% (2/35), which was significantly lower than those of CNS-SLNB and SD-SLNB. The NPV and accuracy was 95.0% and 97.3% for TT-SLNB, respectively. Moreover, a significant relation was seen between the pretreatment clinical T classification and the DR of TT-SLNB (Fisher’s exact test, p= 0.010). Conclusions: TT-SLNB revealed ideal performance in post-NAC ycN0 patients with pretreatment node-positive breast cancers. The application of TT-SLNB reached a better balance between more accurate axillary evaluation and less intervention. Clinical trial information: ChiCTR2000039814.

DR, detection rate; FNR, false-negative rate; NPV, negative predictive value; CNS-SLNB, sentinel lymph node biopsy with single tracer of carbon nanoparticles; SD-SLNB, standardized sentinel lymph node biopsy with dual tracers of radioisotope and blue dye; TT-SLNB, triple-tracer sentinel lymph node biopsy with carbon nanoparticles, radioisotope and blue dye.