Molecular subtype-driven disparities in intraoperative touch imprint cytology accuracy for sentinel lymph node assessment in clinically node-positive breast cancer treated with neoadjuvant chemotherapy

This study aimed to investigate the impact of molecular subtype on the accuracy of intraoperative touch imprint cytology (ITPC) for sentinel lymph node (SLN) evaluation in clinically axillary node-positive (cN +) breast cancer patients treated with neoadjuvant chemotherapy (NAC).

We conducted a retrospective cohort study of 232 cN + breast cancer patients undergoing NAC followed by SLN biopsy with ITPC. Diagnostic performance values (sensitivity, specificity, NPV, false-negative rate, etc.) were calculated against final histopathological diagnosis, and stratified by molecular subtypes.

ITPC identified 53 positive cases (23 false-negatives) across 917 SLNs, demonstrating 69.74% sensitivity, 100% specificity, and 87.15% NPV. HER2-positive (nonluminal) tumors showed the highest tpCR (67.53%) with a moderate SLN-positive rate (24.14%) and the lowest false-negative rate (3.90%). Luminal B (HER2-positive) tumors exhibited a moderate tpCR (57.89%) and a SLN-positive rate (29.31%) but a higher false-negative rate (13.79%). In contrast, both Luminal A and Luminal B HER2-negative displayed lower tpCRs (0.00% and 20.00%), higher SLN-positive rates (66.67% and 57.78%), and higher false-negative rates (33.33% and 22.22%). Notably, TNBC showed a tpCR of 48.98%, a SLN-positive rate of 34.69%, and the lowest false-negative rate of 2.04%. Chemotherapy-induced changes in SLNs (OR = 11.155, 95% CI 2.002-62.152; p = 0.006) and residual micrometastases/ITCs (OR = 37.843, 95% CI 5.031-284.671; p < 0.0001) were independent influencing factors of false-negative results.

Collectively, our study demonstrates that ITPC exhibits a robust accuracy for detecting SLN metastases in cN + breast cancer patients treated with NAC. The findings support the implementation of molecular subtype-specific SLN management: ITPC alone may be adequate for HER2-positive and TNBC tumors; for hormone receptor-positive (Luminal) subtypes, ITPC may need to be combined with molecular/immunohistochemical analysis.