Histopathology · 2026
Heterogeneity of breast and nodal response to neoadjuvant pembrolizumab-based chemoimmunotherapy in early triple-negative breast cancer and its clinical significance.
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Koh Jiwon, Suh Koung Jin, Park Hye Yeon, Kwon Hyun Jung, Sung Hyun-Jung, Ryu Han Suk, Kim Jung Ho, Koh Jaemoon, Lee Kyung-Hun, Lee Dae-Won, Park Changhee, Seo Jeongmin, Chae Heejung, Hwang Woochan, Suh Ye Yoon, Ahn Chang Ho, Im Seock-Ah, Kim Jee Hyun, Park So Yeon
Аннотация
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.
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.