In Triple-Negative Breast Cancer: Correlation Among Metabolic Syndrome, S100A7/cPLA2 Expression and the Efficacy of Neoadjuvant Chemotherapy.

Abstract

Background: Triple-negative breast cancer (TNBC) has a poor prognosis. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a prognostic factor. This study aimed to find predictors of efficacy.

Methods: A total of 266 TNBC patients treated with NAC were included. The relationship between MetS, S100A7/cPLA2 expression and clinicopathological features was investigated. The effect on pCR, clinical response, and disease-free survival (DFS) was observed. A cell co-culture model was established by the researchers to further assess the function of S100A7.

Results: Correlation analysis revealed a strong association between the expressions of S100A7 and cPLA2, with both significantly higher in the MetS group compared to the non-MetS group. Logistic regression analysis indicated that MetS and S100A7/cPLA2 expressions were linked to pCR and clinical response. S100A7/cPLA2 served as an independent predictor of pCR, while cPLA2 was an independent predictor of clinical response. Survival analysis demonstrated that MetS and S100A7/cPLA2 were associated with an increased risk of disease progression. MP grading and clinical efficacy were independent predictors of DFS, with MetS and S100A7/cPLA2 expressions correlating with shortened DFS. In the co-culture model, S100A7 inhibited the NF-κB pathway, enhancing TNBC cell proliferation and invasion in the presence of macrophages, and promoting M2 macrophage polarization.

Conclusion: S100A7/cPLA2 expression predicts a low pCR rate in TNBC patients undergoing NAC and may serve as a potential mechanistic biomarker linking MetS with altered NAC efficacy in TNBC, warranting further investigation and intervention.