Abstract Aim: This cohort study aimed to compare the clinical efficacies between the novel dual tracer composed of indocyanine green (ICG) and blue dye (BD) and the conventional dual tracer composed of radioisotope and BD for sentinel lymph node (SLN) mapping in breast cancer patients. Methods: This study enrolled 471 clinically lymph node-negative patients with primary breast cancer. All the patients received mastectomy, while, for the sentinel lymph node biopsy (SLNB), they were randomized to receive BD plus radioisotope or BD plus ICG. Two hundred and twenty-seven patients received radioisotope plus BD (Control, RB group) for SLNB, while, 200 patients underwent the ICG plus BD (IB group) for SLNB. The detection performances on SLN identification rate, positive SLN counts, detection sensitivity, and false-negative rate were compared between the two groups. Following SLNB, axillary lymph node dissection (ALND) was performed only on patients with metastatic SLNs. Injection safety and potential side-effects of the two dual tracers were evaluated by a 24-month follow-up after the SLNB procedure. Results: In the IB group, 97% (194/200) of the patients who underwent the ICG and BD dual tracer injection showed fluorescent-positive lymphatic vessels within 2-5 minutes. The identification rate of SLNs was comparable between the IB group (99.0%, 198/200) and the RB group (99.6%, 270/271) (P=0.79). No significant differences were observed in identification rate of metastatic SLNs (22.5% versus 22.9%, P>0.05, RB group versus IB group, the same below), positive SLN counts (3.72±2.28 versus 3.91±2.13, P>0.05), positive metastatic SLN counts (0.38±0.84 versus 0.34±0.78, P>0.05), SLNB detection sensitivity (94.4% vs. 92.5%, P>0.05), or false-negative rate (5.6% versus 7.5%, P>0.05) between the two groups. No obvious allergic reaction or anaphylaxis, infection at the injection sites, skin necrosis or distal metastasis was reported in either group during the 24-month follow-up. Conclusions: ICG can be used as a promising alternative tracer for radioisotope in SLN mapping, and when it is combined with BD in lymphangiography, it offers comparable detection sensitivity compared to the conventional lymphatic mapping strategies that are widely used in clinical practice. Efficacy of indocyanine green vs. radioisotope + blue dye for sentinel lymph node mapping in breast cancer patients.Parameters99Tcm-Dx+BD(N=271)ICG+BD (N=200)P-valueSLN identification rate (%)99.6(270/271)99.0(198/200)0.79SLN counts3.91±2.133.72±2.280.09Metastatic SLN rate (%)22.9(62/271)25.5(51/200)0.51Metastatic SLN counts0.34±0.780.38±0.840.46Sensitivity92.5(62/67)94.4(51/54)0.96False-negative rate (%)7.5(5/67)5.6(3/54) Citation Format: Qi X, Yuan L, Zhang Y, Jiang J. Comparison of sentinel lymph node detection performances using methylene blue in conjunction with indocyanine green or radioisotope in breast cancer patients: A prospective single-center cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-01.