Value of breast and axillary tumour-infiltrating lymphocytes for response to neoadjuvant chemo-(immuno)therapy in clinically node-positive breast cancer

Introduction Accurate prediction of pathologic complete response (pCR) after neoadjuvant chemo-(immuno)therapy (NAC) is clinically relevant in clinically node-positive (cN+) breast cancer patients. This study evaluated the association of pre-NAC tumour-infiltrating lymphocytes (TILs) in the breast tumour and axillary lymph node metastases (ALNMs) with breast, axillary, and combined pCR. Second, correlations between pre-NAC breast tumour and ALNM TILs, and between pre- and post-NAC breast tumour TILs were analysed. Methods This retrospective study included cN+ breast cancer patients treated with NAC from the prospective multicentre RISAS trial (NCT02800317). Pre-NAC breast tumour and ALNM TILs and post-NAC breast tumour TILs were centrally assessed and classified as low (<10%), intermediate (10-40%), or high (>40%). Logistic regression, receiver operating characteristic curve, and Spearman's rank correlation analyses were performed. Results Of 206 included patients, 29.6% (61/206) achieved breast pCR, 31.1% (64/206) axillary pCR and 23.3% (48/206) combined pCR. Increased breast tumour TILs were associated with stepwise higher breast (21.4%, 30.4%, 53.1%; p=0.004), and axillary (25.0%, 30.4%, 53.1%; p=0.014) pCR rates for low, intermediate, and high TIL levels. ALNM TILs were not associated with any pCR. Weak-to-moderate positive correlations were found between pre-NAC breast tumour and ALNM TILs ( r s =0.36, p=0.001) and pre- and post-NAC breast tumour TILs ( r s =0.47, p<0.001). Conclusion Pre-NAC breast tumour TILs were associated with breast and axillary pCR, whereas ALNM TILs were not predictive of any pCR in cN+ breast cancer patients treated with NAC. Weak-to-moderate positive correlations were found between pre-NAC breast tumour and ALNM TILs and pre- and post-NAC breast tumour TILs.