This is a retrospective study to evaluate whether the addition of ICG to the widely used MB dye method can improve SLNs recognition in patients with early breast cancer. We concluded that the detection rate of SLNs with the ICG + MB group was significantly higher than that with MB alone (98.5% vs 91.5%). This finding is consistent with earlier research[7, 8].
The ICG + MB mode with a high recognition rate and high accuracy is expected to become a new non-radioactive SLN tracking scheme. The use of alternative radioactive reagents is quite attractive, especially in institutions where radioisotopes are not readily available. Ballardini et al of the European Institute of Oncology reported a trial that compared the tracking ability of indocyanine green and 99mTc in 134 breast cancer patients. The research results of this equivalent design prove that the detection rate of SLNs using the ICG method is not less than 99mTc[9, 10]. Although Ahmed M. criticized the lack of standard dual mapping technology in Ballardini's research, it still showed hope to replace radioactive tracers with indocyanine green[11–13]
We can conclude from this study that the SLNs detection rate of ICG + MB is 7.0% higher than that of MB, which is equivalent to the difference between the double staining method including standard radioisotopes and the single use of dyes, indicating that ICG has a good tracing effect[14, 15]. Although few studies compare the SLNs recognition performance of ICG with that of the nuclide + dye method, we can indirectly conclude that ICG + MB is the most likely alternative method at present[16, 17] .
ICG can not only improve the detection rate of SLNs but also detect more positive SLNs[18]. First, ICG has an extremely high sensitivity to develop some SLNs undetected by MB. This research result shows that the average number of SLNs detected by ICG + MB is 3.1, which is greater than the average number of SLNs detected by the MB method. Similar to previous studies[19]. We hypothesize that the high visibility of ICG's high-resolution near-infrared equipment is what accounts for its exceptional sensitivity. The results of two meta-analyses showed that detecting more SLNs status (3 to 4 nodes) could better understand the status of axillary lymph nodes and was also related to the prognosis of patients, while only one SLN could not fully represent the axillary status[20, 21].
As previously reported, ICG has several limitations. Firstly, the penetration of NIR fluorescence in tissues is lower than γ radial[22]. This will cause a worrying problem. The use of ICG tracing for obese breast cancer patients will lead to the detection failure of SLNs. Although Kitai reported the axillary skin compression technology that has not been used in the current study, there was no significant difference between obese patients (BMI ≥ 25) and non-obese patients[23]. However, Grischke's research result shows that when the patient's BMI is ≤ 40, the detection rate of ICG for SLNs has not been affected. Only when the patient's BMI is > 40, the detection rate of ICG for SLNs will decline[24]. Few Chinese patients have a BMI > 30, which is consistent with the patient information included in this study. Therefore, in China, low penetration of ICG will not become an obstacle to the clinical application[25]. secondly, ICG also has the feature of fluorescence quenching. According to relevant reports, with the increase of ICG concentration, the fluorescence signal of ICG will be quenched (the reduction of fluorescence emission). Mieog recommended 0.62 mg as the optimal injection dose of ICG after the study[26]. However, there is no consensus on the optimal dose of ICG. Based on the previous study, we chose 1.25 mg ICG as the injection dose. The excellent navigation performance showed that the dose could be used clinically. Thirdly, allergic reactions, skin damage, and other adverse reactions are the main factors to be considered in the dye method[27, 28]. In this study, we found no cases of allergy or skin damage. Hypodermic injection rather than intravenous injection may be the main reason for less allergic reaction. The main skin complications included temporary skin staining at the injection site, permanent tattoos, and subcutaneous nodules. Although these skin complications may cause a certain degree of anxiety in patients, they are acceptable for most patients. The safety results are similar to those of the previous meta-analysis[29].
The current study has two shortcomings. On the one hand, we did not compare the ICG + MB method with the 99mTc + MB method. However, the excellent performance of the ICG + MB may be indirectly confirmed by the 5% superiority test. On the other hand, this is a single-center retrospective study, and the results need to be further confirmed by a single-center or multicenter prospective study. In a word, this research result reveals the high detection rate of ICG and the advantages of combining ICG fluorescence with blue dye in the detection of SLN in early breast cancer.