One of the key mechanisms of ADCC-mediated cell death is perforin/granzyme delivery to target cells and subsequent activation of apoptotic cell death.28 We confirmed this by using the perforin inhibitor (concanamycin A, CMA), which causes a significant reversal of cytotoxicity in ADCC-sensitive cell lines (SUM149-Figure 3a, SUM190-Supplementary Figure 4), indicating that granzyme accumulation in tumor cells is essential for ADCC response in this breast cancer subtype. This evidence concerns the gene PRF1 and breast cancer.