Background
This study aimed to evaluate the surgical and oncological impact of intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) in patients with breast cancer with clinically node-negative axilla after neoadjuvant chemotherapy (NACT).
Materials and Methods
Between 2018 and 2023, a retrospective analysis was conducted at a single center (Department of Breast Surgery, Istanbul Faculty of Medicine, Istanbul University), including 154 female patients who were initially diagnosed with cT1 to 4N+ breast cancer and converted to clinically node-negative (cN0) axillary status following NACT. Eligible patients were over 18 years old, female, and without distant metastases at diagnosis or at the time of surgery. Patients were divided into 2 groups: those who underwent intraoperative FS analysis of SLNs (n = 107) and those who did not (n = 47). In the FS group, if SLNs were positive intraoperatively, immediate axillary lymph node dissection (ALND) was performed. In the non-FS group, sentinel lymph node biopsy (SLNB) was performed without intraoperative evaluation, and further management was based on final pathology. SLN counts, number of positive nodes, and pN-ratio (positive/total nodes) were recorded. The frequency of unnecessary ALND and oncological outcomes—particularly disease-free survival (DFS)—were compared. Statistical analyses included independent t tests, chi-square tests, Kaplan-Meier survival curves, and Cox regression models.
Results
A total of 154 patients met the inclusion criteria. Mean age was 49.6 ± 11 years. FS was performed in 69.5% and omitted in 30.5% of patients. There was no significant difference in age, tumor type, or clinical stage between groups. Molecular subtype distribution was similar (P = .113); the most common subtype was hormone receptor–positive/HER2-negative, comprising 50.5% in the FS group and 31.9% in the non-FS group. In the FS group, 16 patients (15%) underwent simultaneous ALND based on frozen results, yet 8 of these showed no metastatic lymph nodes in final pathology. Only 2 patients (1.3%)—1 in each group—underwent delayed ALND. Final pathology revealed residual metastatic axillary nodes (ypN+) in 43% of the FS group and 34% of the non-FS group. There was no significant difference in SLN counts (3.51 ± 1.66 vs 3.49 ± 1.93), non-SLN counts (2.49 ± 1.38 vs 2.45 ± 1.70), or number of positive nodes (1.64 ± 0.87 vs 1.93 ± 0.92) between groups. After a median follow-up of 38 months, rates of local recurrence (2.6%; n = 4), distant metastasis (8.4%; n = 13), and cancer-related death (3.9%; n = 6) were observed. All local recurrences, deaths, and cases of lymphedema (n = 3) occurred exclusively in the FS group, although these were not statistically significant. Lower distant metastasis rates were seen in the non-FS group (2.1% vs 11.2%; P = .111), but this group had a shorter median follow-up duration (29 vs 50 months).
Conclusion
Routine intraoperative FS analysis of SLNs in patients with clinically node-negative axilla following NACT does not provide additional surgical benefit. On the contrary, this practice led to unnecessary ALND in over 50% of intraoperatively positive cases, increasing the risk of morbidities such as lymphedema. In patients without FS, comparable oncological outcomes were achieved using SLNB alone (with selective use of targeted axillary dissection when needed). These findings support the de-escalation of axillary surgery in clinically node-negative patients after NACT. Avoiding routine FS and immediate ALND in appropriately selected patients can maintain oncologic safety while reducing surgical burden and morbidity.
