Axillary lymph node dissection has long been used in women with axillary nodal metastases. It is effective for maintaining regional control but is also associated with a significant risk of several complications, such as lymphedema, and numbness.14. As a less invasive alternative, SLNB has been gradually performed in an increasing number of breast cancer patients. Its efficacy has been verified in several large clinical trials. The ACOSOG Z0011 trial enrolled eligible patients with clinical stage T1 or T2 invasive breast cancer, with no palpable axillary adenopathy, and with 1 or 2 sentinel lymph nodes containing metastases11.With a median follow-up of 9.3 years, SLND alone was not inferior to ALND in terms of both overall survival and disease-free survival. The NSABP B-32 trial also confirmed that regional control, overall survival and disease-free survival were equivalent between the SLNB alone group and the SLNB with axillary dissection group. Therefore, if applied properly, SLNB can benefit patients similar to ALND while inducing less morbidity15.
Furthermore, we must emphasize that the premise for choosing SLNB rather than ALND is its accuracy for representing the status of the axilla. Only when precision is guaranteed can SLNB be used to direct doctors to stage the axilla and to design a strategy according to the treatment plan. We wondered whether intraoperative tumor biopsy would have an effect on the anatomy of lymphatic channels and lead to less reliable SLN detection. In this regard, we studied the number of SLNs found during surgery and the false-negative rates in preoperative and intraoperative tumor biopsy groups. All the enrolled patients underwent SLN biopsy using a combined tracer of blue dye and radioisotope. Based on our results, preoperative tumor biopsy could detect more SLNs than intraoperative biopsy. We attributed this disparity to the anatomical alterations in lymphatic channels caused by intraoperative excisional tumor biopsy. Since tumor excision during surgery is more invasive than preoperative core needle biopsy, it may seriously destroy the lymphatic channels and result in fewer SLNs identified. Another reason may be the aseptic inflammation caused by preoperative tumor biopsy. When a patient receives a preoperative tumor biopsy, aseptic inflammation can be induced, and macrophages can be activated by inflammation. Therefore, more blue dye can be more easily phagocytosed by macrophages and transferred to lymphatic channels. Finally, more blue dye can be taken into the sentinel lymph nodes. The number of SLNs sent for histology tests plays a significant role in evaluating the axillary status. One critical reason is that the sentinel node number is potentially associated with the risk of being unable to recognize a positive SLN. The study by Robbins16 corroborated this theory; he demonstrated that SLN positivity was significantly greater when two or more SLNs were found than when only a single SLN was found (34% versus 18%, P=0.003). Although several previous studies have supported the significance of detecting all radioisotopes or blue dye-containing lymph nodes and have emphasized this concept from the "more is better" viewpoint, there is no consensus on how many SLNs must be removed to accurately predict lymph node status16-18.One paper showed that removing up to 5 SLNs was adequate to find metastatic carcinoma in more than 99% of patients, indicating that surgeons can stop the dissection after removing 5 SLNs19. However, the data of another paper found that although 98% of positive SLNs were identified within the first three SLN sites, the remaining patients had their first positive SLNs identified at sites 4 to 8. Therefore, the authors suggested that there was no absolute upper threshold for the number of SLNs that should be removed and that SLNB should not be performed until all hot nodes are detected and removed. Robbins also favored attempts to identify all potential SLNs to avoid failure in recognizing a positive SLN16. In our study, since some of the recruited patients underwent axillary lymph node dissection, we verified the accuracy of SLNB. We observed false negative rates were 3% and 18% (p=0.039) in the preoperative and intraoperative biopsy groups, respectively. Therefore, our results were in accordance with those of other studies, showing that the false-negative rate decreased as the number of removed SLNs increased. For instance, one study21 showed that the false-negative rate was 26.6% for a single SLN, while it decreased to 0% when 4 or more SLNs were removed.
As shown above, with regard to the identified SLN number, patients benefited more from preoperative than from intraoperative tumor biopsy. Furthermore, we performed subgroup analysis when taking several clinical parameters into consideration. Tumor position, T stage, patient age, and duration between tumor biopsy and breast surgery were included in the subgroup analysis. We found that when tumors were located in the outer quadrant, in stage T2 or T3 tumors, or when patients were older than 50 years, the difference in identified SLN numbers between the preoperative biopsy group and the intraoperative group was significant. Therefore, we suggest that under the above conditions, preoperative tumor biopsy is superior to intraoperative biopsy. In addition, we emphasize the necessity of preoperative tumor biopsy as the first choice when there are fewer than 7 days between biopsy and breast surgery. Because when the interval was longer than 7 days, no significant difference in the number of SLNs could be observed.
In conclusion, we observed that preoperative tumor biopsy could detect more SLNs than intraoperative tumor biopsy. In addition, the false-negative rate was lower in the preoperative tumor biopsy group than in the intraoperative biopsy group.
Therefore, we advise surgeons to choose preoperative biopsy when tumor biopsies are considered for improving the accuracy of SLNB.