AXINEO: AXIllary response to NEOadjuvant chemotherapy for breast cancer: can we predict response based on a biomarker panel?

BACKGROUND: Up to 60% of breast cancer patients achieve pathological complete response (pCR) and factors associated with breast pCR have been extensively investigated. In patients with initially node-positive disease predicting axillary response to treatment remains challenging. Our study examines a biomarker panel assessed on core-biopsy lymph-node metastatic tissue with the goal to establish predictive markers for nodal positive breast cancer. MATERIALS AND METHODS: Forty women with core biopsy-proven node-positive breast cancer scheduled to receive neoadjuvant treatment at the certified Breast Cancer Center of the University Hospital Schleswig-Holstein Campus Lübeck were included. The expressions of CAIX, PD-L1, TROP2, MSH2, MSH6, MLH1, and PMS2 as well as p53 mutation were assessed. Biomarkers were chosen based on their association with tumorigenesis and tumor progression. Statistical analysis was performed using SPSS 29. This investigator-initiated study was supported by a research grant from Gilead (Gilead Förderprogramm). RESULTS: Higher CAIX levels were associated with triple-negative and Her2-positive receptor status (p = 0.003), Ki67 ≥ 50% in breast core biopsy (p = 0.005), as well as postmenopausal status (p = 0.007). P53 mutation was more frequent in G3 tumors (p = 0.025). All lymph-node metastases were microsatellite stable (MSS). None of the markers could significantly predict pathological response (complete, breast, or nodal). CONCLUSION: Our study shows upregulated CAIX in lymph-node metastasis frequently occurs in aggressive and highly proliferative tumors. However, none of the examined biomarkers could predict nodal response to therapy. Further research is necessary to better identify patients most likely to achieve nodal response through neoadjuvant chemotherapy.