Triggering receptors expressed on myeloid cells (TREM-1) and TREM-2 as predictors of pathological complete response to neoadjuvant therapy in triple-negative breast cancer.

Abstract

Background: Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, characterized by early metastasis, high recurrence rates, and limited targeted therapy options. Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a well-established prognostic surrogate for long-term outcome, yet reliable predictive biomarkers remain elusive. TREM-1 and TREM-2 are key immune modulators that shape the balance between proinflammatory and immunosuppressive signaling within the tumor microenvironment (TME). This study aimed to evaluate the predictive utility of TREM-1 and TREM-2 expression for pCR in TNBC after NACT.

Methods: Pre-treatment biopsies from 71 patients with early or locally advanced TNBC treated with chemotherapy-based NACT were analyzed by immunohistochemistry (IHC) for TREM-1 and TREM-2. Stromal/TIL H-scores were used for the final analysis. Clinical records were reviewed for treatment regimen. Cutoff values were determined using receiver operating characteristic (ROC) analysis based on the Youden index, and multivariable logistic regression was used to identify independent predictors of pCR.

Results: High stromal TREM-1 expression (> 90) independently predicted higher pCR rates (OR 12.25; p = 0.003), whereas high stromal TREM-2 expression (> 10) correlated with lower pCR likelihood (OR 0.105; p = 0.030). The predefined high Ki-67 group and lower T-stage also predicted pCR. In secondary analyses, tumor-cell TREM-1 and TREM-2 expression were not significantly associated with pCR.

Conclusion: The opposing associations of stromal TREM-1 and TREM-2 with pCR suggest that the TIL-mediated tumor microenvironment may play an important role in shaping treatment sensitivity in TNBC. High TREM-1 expression is linked to an inflammatory, treatment-responsive phenotype, whereas high TREM-2 expression reflects an immunosuppressive, resistant state. Their combined evaluation may provide clinically meaningful insights for predicting therapeutic response and for developing novel immunomodulatory strategies in TNBC.