Chromosome 1q21.3, encoding IRAK1, is amplified in recurrent BC; S100A7/8/9 and IRAK1 drive tumorsphere growth, disrupted by pacritinib via IRAK1, not JAK2; pacritinib TGI in xenograft models via IRAK1; pacritinib + paclitaxel caused durable tumor regressions in a neoadjuvant TNBC model. Here, IRAK1 is linked to breast cancer.