Quantitative and spatial distribution characteristics of CD66b+ tumor-associated neutrophils in metaplastic and non-metaplastic triple-negative breast cancer treated with neoadjuvant therapy and their prognostic significance.

PURPOSE: This study aimed to compare the density and spatial distribution of tumor-associated neutrophils (TANs) in metaplastic breast cancer (MpBC) and non-metaplastic triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NACT) to identify prognostic biomarkers and therapeutic implications.

METHODS

We conducted a retrospective analysis of patients with MpBC and non-metaplastic TNBC both treated with NACT from three hospitals. CD66b+ TANs were quantified and spatially mapped using an artificial intelligence (AI) -based positive cell classifier. Clinicopathological characteristics were compared between the two groups. Statistical analyses were used to assess the prognostic value of TANs and their predictive value in NACT.

RESULTS

Significant differences were observed between MpBC and non-metaplastic TNBC patients in age, tumor size, Ki-67 expression, residual cancer burden grade, pathologic complete remission (pCR) rate, disease-free survival (DFS), CD66b+ TAN density, and spatial distribution. No MpBC patients achieved pCR, whereas 30.8 % of non-metaplastic TNBC patients did. In MpBC, larger tumor size and stromal-predominant CD66b+ TAN distribution were associated with poorer prognosis. In non-metaplastic TNBC, tumor size > 2 cm, androgen receptor positivity, and high CD66b+ TAN density correlated with lower pCR rates, while tumor size > 2 cm, lymph node positivity, and elevated CD66b+ TAN density were linked to worse DFS.

CONCLUSION

CD66b+ TANs might serve as a potential prognostic biomarker in MpBC and non-metaplastic TNBC following NACT, and their density and spatial distribution also contributed insights into the prognosis of the patients.