The primary goal of intraoperative FS is to prevent reoperation for ALND. According to the ACOSOG Z0011 trial, an ALND is indicated only when the SLNB results in 3 or more nodes positive for metastatic disease [9]. Therefore, SLN intraoperative FS do not provide benefit in patients who have only 1 or 2 nodal metastases. Even with routine intraoperative FS, ALND as a second surgical procedure is still required if the intraoperative FS turns out to be a false negative. The false negative rate of having more than 2 SLNs on FS is still unclear. However, a study conducted at Imam Khomeini hospital, Iran, revealed a false negative rate of 20.6% when comparing intraoperative FS to PS [8]. Out of those cases, 4 cases (3.9%) were found with 3 or more diseased nodes. Therefore, using SLNB with FS resulted in a reoperation rate of up to 4%. Moreover, there were some limitations to the routine practice of sending FS. It is an expensive and time-consuming procedure which requires an experienced pathologist, additionally the preparation process could result in irreversible tissue loss which could ultimately alter the final pathological diagnosis such as understaging micrometastatic disease. Research have found that intraoperative FS was not sufficient to rule out micrometastases [17,18]. After the implementation of the ACOSOG Z0011 trial, other studies also recommended the usage of PS in early-staged breast cancer patients who meet the ACOSOG trial criteria and discouraged the routine use of intraoperative FS for similar reasons [8,11,19].
In this retrospective review, given that ALND is mandatory in patients with at least 3 SLNs with metastatic disease, we found that patients with early-staged breast cancer meeting the ACOSOG Z011 trial criteria undergoing SLNB with PS alone had a reoperation rate of 0%. This matches findings from previous study which demonstrated that PS alone resulted in a small number of additional ALND (1.9%) [11]. Therefore, the practice of intraoperative FS does not necessarily prevent the second ALND operation compared to SLNB without FS. Three or more SLNs were detected in 72.0% of cases with an average of 4.15 nodes per case, which is comparable to the optimal yield of SLNs for SLNB (4 SLNs per case) [20]. When 2 or more SLNs are identified, the false negative rate can be decreased to an acceptable 5% level [20] as recommended by the American Society of Clinical Oncology (ASCO) guidelines [3].
In our descriptive retrospective series, the negative predictive value of a radiological negative node appears to be better than the positive predictive value of positive nodes, as up to 92.6% of patients with radiological negative nodes had no metastasis on final pathology. Furthermore, there was a statistically significant association between radiological nodal status and nodal positivity. This finding is consistent with prior studies which stated that ultrasonography and mammography (the imaging modalities in our study), have a strong predictive value for nodal positivity in early-staged breast cancer with non-palpable axillary nodes [21–23]. As for tumor clinicopathology, there was no statistically significant correlation between SLN metastasis and tumor size (p = 0.095) despite the percentage of patients with SLN metastasis in the T2 group was clearly higher than that of the T1 group. This is likely due to the fact that tumor sizes in the T2 group were close to the lower limit of 2 centimeters and likewise, the tumors in the T1 group were close to the upper limit of the T stage. This finding is inconsistent with a previous study which found that the rate of nodal metastases increased as the tumor size increased [24–27]. The percentage of patients with positive SLNs in the histologic grade 2 and 3 groups was higher than that in the histologic grade 1 group. Nodal positivity increased in accordance with histologic grading. However, there was no significant association between the higher histologic grade and nodal positivity in our study, even though Ding et al. previously found that histologic grade was one of the three independent predictive factors for positive SLN [22]. Our series also suggested that
lymphovascular invasion could be useful as a predictor for nodal positivity with a markedly significant association with SLN metastasis (p < 0.001). Moreover, the absence of lymphovascular invasion may be an indicator for nodal negativity, as 95.5% of patients without lymphovascular invasion were also found to be negative for nodal metastases. This is consistent with a systematic review and meta-analysis which found that lymphovascular invasion was a valuable predictor of lymph node metastasis [25]. The association of hormonal receptor status and SLN metastasis is still currently controversial. Prior studies suggested that estrogen receptor status may be useful as a predictor for nodal positivity and also discouraged the use of other hormonal receptors such as HER2 expression and histologic grading for predictive purposes [28,29] On the other hand, a study conducted in Germany suggested that progesterone receptor and HER2 status can correctly predict nodal metastasis [30]. However, we did not find any of these associations in our case series, as none of the hormonal receptor statuses were found to have any significant correlation with SLN metastasis.
Our study demonstrated that in certain well-selected cases, the practice of SLNB with PS alone was not inferior to SLNB with routine FS in terms of reoperation rate. Moreover, in terms of cost effectiveness, the practice of PS alone could reduce the costs of up to 1160 baht or approximately 37 US dollars per case, which is a significant amount of money, especially in low to middle income countries (LMICS). Radiological nodal status and lymphovascular invasion of the main tumor can be used as predictors of nodal metastasis, which provide a better nodal positivity prediction compared to other clinicopathology. Limitations to this study are the small sample size with data from a single hospital. Additionally, this study was a retrospective review which could lead to selection bias. However, despite these limitations, this study is important because it is the first report to provide the reoperation rate in SLNB without FS in Thailand and suggested that such practice is not inferior to the current practice of routine intraoperative FS in patients with early-stage breast cancer and non-palpable axillary nodes. Finally, we encouraged a national data collection on tumor clinicopathology and radiological nodal statuses as associated tendencies for nodal metastasis need further study but can be incorporated into a SLNB with PS alone practice.