In the present study, we found that only a small proportion of patients (1.6%) required additional re-excision after the initial sample and first re-excision were both positive, and whether the patient decided to convert to mastectomy was not dependent on the results of the re-excised margin. However, the positive re-excision margin rate was higher in patients with the DCIS histological type than in patients with invasive carcinomas. These results suggest that while the value of intraoperative frozen section analysis in re-excised margins may be limited in the general population of patients undergoing attempted BCS, this process may be useful in specific subgroups of patients, such as those with the DCIS histological type.
The success of BCS relies on the achievement of negative margins. Leaving tissue adjacent to a positive excised margin in situ significantly increases the risk of ipsilateral breast cancer recurrence in both invasive disease and DCIS. Consequently, during BCS, a sample with a positive margin should prompt surgical re-excision [11–13]. In 2014, the Society of Surgical Oncology and the American Society for Radiation Oncology established consensus guidelines on margins for BCS that stated there should be “no ink on the tumor”, meaning that the margin should be completely clear, and although this change in standards did lead to a 16% reduction in additional surgeries after initial lumpectomy, 22% of patients treated with BCS have been found still to require additional surgery . In the present study, 603 of 727 patients (82.9%) underwent a single intraoperative FME that showed a margin-free status. Based on the current standards, our results indicate that the remaining patients (17.1%) in whom the initial FME was not negative would have been at a higher risk of needing to undergo additional re-operation after the initial lumpectomy if intraoperative FME had not been available in our institution.
Trials have consistently shown that frozen section analysis decreases the rate of reoperations for margins, and the impact of intraoperative margin management options is greatest in populations in which the baseline rates of inadequate margins are high . Furthermore, while studies have suggested that frozen section analysis should always be considered except in populations in which the reoperation rate is already low (15%), the significance of the impact of this procedure has remained unclear in populations with baseline re-operation risk rates that fall below 20% . In the present study, the baseline rate of inadequate margins was 17.1%, and 15.4% of all patients underwent a single margin re-excision procedure that resulted in a margin-free status after the initial frozen margin was positive. These results indicate that 98.4% of the patients in this study may have avoided a re-operation due to a positive margin because the initial resection margin was evaluated by frozen section analysis, allowing them to undergo re-excision. These results are in accordance with a previous study reported by Chen et al., who found that 16% of patients with an initially positive margin underwent intraoperative re-excisions and ultimately achieved successful BCS; the surgical treatment, margin management strategy and frozen section analysis used in their study were quite similar to those used in ours . Together, these findings indicate that using intraoperative frozen section analysis for initial resection margin evaluation revealed that some patients had positive margins, thus allowing re-excision, which could reduce the reoperation rate in populations in which the baseline rate of inadequate margins is lower than 20%.
The value of intraoperative FME for identifying margins that should be re-excised has rarely been studied. Jorns et al reported that use of FME for reexcision specimens resulted in no difference in the need for further reexcision or ultimate conversion to mastectomy because of a similar high false negative rate of FME in re-excision specimens (13%) as compared with that of lumpectomy series (10%) . Based on these findings, the authors suggested that FME may not provide added value for patients undergoing reoperation for margins. Even so, most hospitals in China choose intraoperative frozen section analysis for margin evaluation, and in our institution, intraoperative FME for re-excision of margins is routinely conducted ( a cavity-shaving procedure is not generally performed even though this procedure has been associated with a lower rate of positive margins in a prospective randomized trial and multiple cohort studies ). In the present study, we found that in 98.4% of attempted BCS patients (82.9% with initially margin free and 15.4% with a single margin-free re-excision), the risk of reoperation was either verified to be low or actually lowered as a result of the initial frozen tissue resection margin evaluation. Because only twelve patients (1.6%) in this study required an additional margin re-excision after the first re-excised margin was positive, we suggest that FME at re-excision margins could be omitted if cavity shaving, which is recommended for re-excised margins, is always performed after the initial margin evaluation. Secondly, the rate of positivity for re-excision margins was 9.6% in our study, which is similar to previously published false-negative rates reported for FME in re-excision specimens (ranging from 3.5–13%). It is therefore possible that the re-operation rate may not be reduced by the intraoperative evaluation of frozen sections of re-excised margins. Our results also reveal that a large proportion of the patients (72.7%) with a positive initial margin converted to mastectomy, and that only a small proportion of these patients (3%) converted to another therapy based on this result. These results collectively demonstrate that FME for re-excision margins may not influence surgical decisions during BCS.
Several studies have constructed nomograms to predict the likelihood of having positive initial margins during BCS and have significantly associated the DCIS histological type with initial margin positivity [21.22]. However, the risk factors for re-excision margin positivity have rarely been reported. In the present study, there was a greater increase in the proportion of patients with the DCIS histological type in the re-excision margin-positive group than in the re-excision margin-negative group and in patients who converted to mastectomy than in those with successful partial mastectomy (data not shown). The multivariate analysis also showed that the DCIS histological type was an independent risk factor for re-excised margin involvement in patients undergoing BCS. These data demonstrate that the subgroup of patients with the DCIS histopathologic type is associated with a reduced ability to acceptable margin status, and intraoperative FME of re-excision specimens may therefore be valuable in this subgroup of patients.
In conclusion, although the present study represents a retrospective analysis, our results show that while routine intraoperative frozen section analysis of re-excised margins may have limited value in the general population undergoing BCS, this process could benefit patients with the DCIS histological type undergoing this procedure.