Heterogeneity of breast and nodal response to neoadjuvant pembrolizumab-based chemoimmunotherapy in early triple-negative breast cancer and its clinical significance.

AIMS: To characterize the heterogeneity of pathological responses in the breast and regional lymph nodes after neoadjuvant pembrolizumab-based chemoimmunotherapy in early-stage triple-negative breast cancer (TNBC) and to explore their clinical implications.

METHODS AND

RESULTS

A total of 203 patients with TNBC treated with neoadjuvant chemotherapy combined with pembrolizumab followed by surgery were included. Histopathological features of baseline biopsy and post-treatment specimens, including residual carcinoma patterns and tumour-bed features, were systematically reviewed and correlated with treatment response and clinical outcomes. Pathological complete response (pCR) was achieved in 63.1% of patients. Higher histological grade, increased tumour-infiltrating lymphocytes (TILs), and higher Ki-67 labelling index were independently associated with pCR. Residual carcinoma patterns and tumour-bed changes were heterogeneous, with residual disease most commonly presenting as a solitary, confined focus (51.4%). Fibrotic tumour beds were more frequently observed in non-pCR cases, whereas stromal elastosis was enriched among pCR cases. Nodal responses were also heterogeneous, including complete nodal response (23.6%), non-response (8.4%), and mixed nodal response (7.4%). Disease recurrence was more frequent among patients without pCR, and among those with multifocal baseline tumours, higher cT stage, rare histological subtypes, low TILs and residual nodal disease.

CONCLUSIONS

This real-world study provides a comprehensive pathological characterization of breast and nodal responses after neoadjuvant chemoimmunotherapy in early TNBC, highlighting heterogeneity beyond pCR and ypN staging and offering a more detailed characterization of treatment-response patterns.