Intraoperative Frozen Section Analysis After Neoadjuvant Chemotherapy Leads to Unnecessary ALND in Node-Negative Breast Cancer Patients
Key Insights
A single-center retrospective study of 154 breast cancer (search) patients found that intraoperative frozen section analysis of sentinel lymph nodes after neoadjuvant chemotherapy (search) did not provide additional surgical benefit.
Among patients who underwent frozen section, 15% received immediate ALND, yet half of these showed no metastatic lymph nodes on final pathology, indicating unnecessary extensive surgery.
All local recurrences, cancer-related deaths, and lymphedema cases occurred exclusively in the frozen section group, though differences were not statistically significant.
A retrospective study from Istanbul University has found that routine intraoperative frozen section (FS) analysis of sentinel lymph nodes (SLNs) in breast cancer (search) patients who convert to clinically node-negative status after neoadjuvant chemotherapy (search) (NACT) does not confer additional surgical benefit and, in fact, leads to unnecessary axillary lymph node dissection (ALND) in a substantial proportion of cases.
The study, conducted at the Department of Breast Surgery, Istanbul Faculty of Medicine, analyzed 154 female patients between 2018 and 2023 who were initially diagnosed with cT1–4N+ breast cancer (search) and subsequently converted to clinically node-negative (cN0) axillary status following NACT. Patients were divided into two groups: those who underwent intraoperative FS analysis of SLNs (n = 107, 69.5%) and those who did not (n = 47, 30.5%).
Frozen Section Leads to Unnecessary ALND
Among the 107 patients in the FS group, 16 (15%) underwent simultaneous ALND based on intraoperative frozen results. However, final pathology revealed that 8 of these patients—half of those taken for immediate ALND—had no metastatic lymph nodes whatsoever. This means that over 50% of intraoperatively positive cases resulted in unnecessary, more extensive axillary surgery.
Only 2 patients (1.3%) across the entire cohort—one in each group—underwent delayed ALND based on final pathology results, underscoring that the vast majority of surgical decisions driven by frozen section analysis were made in the operating room.
Comparable Pathological and Oncological Outcomes
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 between groups 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).
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 across the full cohort. Notably, all local recurrences, all cancer-related deaths, and all cases of lymphedema (n = 3) occurred exclusively in the FS group, although these differences did not reach statistical significance.
Lower distant metastasis rates were observed in the non-FS group (2.1% vs 11.2%; P = .111), but the researchers caution that this group had a shorter median follow-up duration (29 months vs 50 months), which may confound the comparison.
Patient Demographics and Molecular Subtypes
The mean patient age was 49.6 ± 11 years. There was no significant difference in age, tumor type, or clinical stage between the two groups. Molecular subtype distribution was similar (P = .113), with the most common subtype being hormone receptor–positive/HER2-negative, comprising 50.5% in the FS group and 31.9% in the non-FS group.
Supporting Evidence from Targeted Axillary Dissection Research
These findings align with emerging evidence questioning the necessity of aggressive axillary surgery in the post-NACT setting. A separate retrospective review presented at the same forum examined 87 patients who underwent targeted axillary dissection (TAD) with SLNB for initially node-positive breast cancer (search) after NACT. That study found that 28% of patients with positive nodes after NACT showed no uptake of radiotracer or blue dye, meaning the clipped node would have been missed without localization. Despite only 12% of patients undergoing ALND, no axillary recurrences were observed (n = 86/87, with one patient lost to follow-up).
Seven patients (8%) in the TAD cohort experienced distant metastasis, with a median time to diagnosis from surgery of 16.5 months (IQR, 12–29). Of these, four had positive nodes on final pathology but did not undergo ALND.
Clinical Implications
The Istanbul researchers conclude that routine intraoperative FS analysis of SLNs in clinically node-negative patients following NACT does not provide additional surgical benefit and instead increases the risk of morbidities such as lymphedema through unnecessary ALND. They advocate that in patients without FS, comparable oncological outcomes can be 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," the authors state. "Avoiding routine FS and immediate ALND in appropriately selected patients can maintain oncologic safety while reducing surgical burden and morbidity."
The study adds to the growing body of evidence that surgical practice is outpacing clinical trial data, with surgeons increasingly omitting ALND. As the authors of the TAD study note, the field awaits data from large clinical trials such as Alliance A011202 to further clarify optimal axillary management in this patient population.