Single-Cell Immune Signature and Response to Neoadjuvant Chemotherapy in BRCA1/2 -Mutated Breast Cancer

PURPOSE: -mutated breast cancer is largely unknown and whether an immune signature on the basis of single-cell atlas is associated with response to neoadjuvant chemotherapy remains to be investigated. MATERIALS AND METHODS: carriers with operable primary human epidermal growth factor receptor 2-negative tumors who received neoadjuvant chemotherapy, and the associations between immune cell subtypes defined by scRNA-seq and pathologic complete response (pCR) were investigated. RESULTS: carriers, 36.2% achieved a pCR. We established an immune signature on the basis of the single-cell and bulk RNA-seq data, named BRCA-IM. The BRCA-IM model exhibited an excellent prediction of pCR in the neoadjuvant chemotherapy cohort, with AUC values of 0.81(95% CI, 0.69 to 0.92) in the training set and 0.91(95% CI, 0.79 to 1.00) in the test set, respectively; and the BRCA-IM model remained as an independent predictor for pCR after adjusting for other factors. Moreover, higher BRCA-IM scores were significantly associated with more favorable survival in the neoadjuvant chemotherapy cohort. CONCLUSION: -mutated tumors.