The primary goal of intraoperative FS is to prevent reoperation for ALND. According to the ACOSOG Z0011 trial, an ALND is indicated only when SLNB results in 3 or more nodes positive for metastatic disease . Therefore, intraoperative FS do not provide benefit in patients with only 1 or 2 nodal metastases. Even with routine intraoperative FS, ALND as a second surgical procedure is required if the intraoperative FS was later confirmed to be a false negative. The false negative rate of having more than 2 SLNs positive on FS is still not well defined. However, a study conducted at Imam Khomeini hospital, Iran, revealed a false negative rate of 20.6% when comparing intraoperative FS to PS . Out of those, 4 cases (3.9%) were found with 3 or more diseased nodes. There are also important limitations to the routine practice of sending FS. It is an expensive and a 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. Studies have also found that intraoperative FS was not sufficient to rule out micrometastases [17, 18]. Other studies also recommended the use of PS only in early-stage breast cancer patients who satisfy the ACOSOG trial criteria and discouraged the routine use of intraoperative FS [8, 11, 19].
In this retrospective study, given that ALND is mandatory in patients with at least 3 positive SLNs, we found a reoperation rate of 0% when using PS alone in patients with early-stage breast cancer meeting the ACOSOG Z011 criteria. Previous studies demonstrated that PS alone resulted in a small number of additional ALND (1.9%) . Therefore, the practice of intraoperative FS does not necessarily prevent the second ALND operation compared to SLNB without FS. Three or more SLNs were retrieved 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) . When 2 or more SLNs are identified, the false negative rate decreases to an acceptable 5% level as recommended by the American Society of Clinical Oncology (ASCO) guidelines [3, 20]. Breast cancer nomograms have been widely used to predict sentinel lymph node metastasis. One of the first and most validated models is that by Van Zee et al., from the Memorial Sloan-Kettering Cancer Center (MSKCC). The nomogram identified 8 clinicopathological variables that were associated with SLN positivity: age, tumor size, tumor type, tumor location, lymphovascular invasion, multifocality, estrogen receptor status and progesterone receptor status . Other studies supported the MSKCC nomogram findings that age, tumor size, histopathology, estrogen receptor status and progesterone receptor status were valuable predictors of SLN status [22, 23]. A study from Thailand demonstrated that the MSKCC nomogram could accurately predict the probability of SLN metastasis for Thai breast cancer patients, however, only tumor size, histopathology, location, lymphovascular invasion, multifocality and progesterone receptor status were found to be significantly associated with SLNs metastasis . In our descriptive retrospective series, a radiolographically negative nodal status and lack of lymphovascular invasion appear to be negative predictors of lack of SLN metastasis. This finding is consistent with prior studies which found that ultrasound and mammogram findings have a strong predictive value for nodal positivity in early-stage breast cancer with non-palpable axillary nodes [25,26,27]. Our series suggest that lymphovascular invasion could be a useful predictor that could be added to the breast cancer after further validation. It is notable that HER2 positivity, which represents a highly aggressive tumor subtype, was not associated with nodal metastasis. The inclusion of 10 cases with equivocal HER2 statuses may have altered the statistical outcome. We propose that further research could lead to the integration of lymphovascular invasion presence and radiographic findings into predictive nomograms specific to the Thai breast cancer patient.
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 cost of up to 1,160 baht or approximately 37 US dollars per case, which is especially important in the context of low-to-middle income countries (LMICs). Radiolographic nodal status and lymphovascular invasion of the main tumor can be used as predictors of nodal metastasis, which provide a higher nodal positivity prediction compared to other clinicopathology. Our study has a lower percentage of positive nodes after SLNB than that reported elsewhere in the literature. The lower node positivity on SLNB may be attributed to the fact that in 2016 to 2018 time period, surgeons at our center still perform ALND for cases with 1 positive FNA result, as recommended by the 2018 NCCN guidelines and these patients were consequently excluded from the study. However, this practice was changed in the 2019 NCCN guidelines, as now, SLNB can be considered even when FNA results were positive with a few suspicious nodes on imaging. Moreover, our center is a tertiary healthcare center, where strict axillary ultrasound screening is routinely performed, thus more positive nodes were being detected by FNA and these cases with preoperative positive nodes were excluded from our study. This study also included only breast conservative therapy cases, therefore average tumor size is smaller than many other studies (T1 more than 60% of the cases).
However, despite these limitations, this pilot study describes the reoperation rate of SLNB without FS in Thailand. We suggest 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 encourage a prospective national data collection on tumor clinicopathology and radiolographic nodal status to provide predictive ability, especially in the context of PS utilization alone.