Work

Identification of serum proteins associated with response of triple-negative breast cancer to neoadjuvant chemotherapy: preliminary results from the INSTIGO trial

Year: 2025

Type: article

Abstract: BACKGROUND: Triple-negative breast cancer (TNBC) is a breast cancer subtype with the highest recurrence rates, for which response to neoadjuvant chemotherapy (NACT) is a critical prognostic factor. Liquid biopsy (LB) is an emerging approach in the personalization of TNBC management; among the numerous circulating molecules assessable by LB, serum proteins are gaining interest, owing to their multiple roles in cancer progression and anti-cancer immune response. Here we report findings of interim analyses in the INSTIGO trial, which aims to discover circulating protein biomarkers of TNBC response to NACT. PATIENTS AND METHODS: technology). RESULTS: Among the 24 analysable patients, 13 had pathological complete response (pCR) and 11 were without pCR. In the pCR group, mean CX3CL1, angiopoietin-2 (ANGPOI-2), CD40 and PD-L1 levels increased significantly after NACT (p < 0.001, p < 0.001, p = 0.006, and p = 0.02, respectively). In the non-pCR group, mean CXCL5 level tended to decrease after treatment (p = 0.06). When the difference in protein levels between the end and the start of NACT was measured for each patient (Δ of a given protein), ΔCX3CL1, ΔCXCL5 and ΔANGPOI-2 differed significantly between pCR and non-pCR patients (p = 0.003, p = 0.04, p = 0.04, respectively). The baseline concentrations of CCL5, IL8, TIE2, CX3CL1 and CXCL5 tended to be associated with response to NACT, with higher levels observed among the non-pCR patients; however, statistical significance was not reached. CONCLUSION: Our findings highlight the potential of circulating proteins to be biomarkers of TNBC response to NACT. Pre/post-NACT changes in CX3CL1, CXCL5, CD40, ANGPOI-2 and PD-L1 levels suggest their relevance for assessing NACT efficacy. These results will be validated at completion of the INSTIGO trial. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04438681.

Source: Clinical Proteomics

DOI: 10.1186/s12014-025-09574-0