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Figure 2. SIAH marks proliferating tumor cells at a single-cell resolution, and SIAH is a therapy-responsive and prognostic biomarker that can be used to risk-stratify incomplete responders in NACT/NST-treated high-risk and locally advanced breast cancer. IMPAX stands for the IMPAX digital mammography, a powerful diagnostic platform for breast imaging at the Sentara Breast Centers. (A) pCR is a good prognostic marker associated with long-term survival post-NACT/NST. However, for the pIR patients with residual disease, additional tools are needed to distinguish which patients are at high risk for early tumor relapse and thus who may need additional adjuvant chemotherapies. (B) The pIR patients with no or low SIAH expression in residual tumors post-NACT/NST stayed in remission and have prolonged survival (examples: patients #82 and #28). (C) In contrast, the pIR patients with persistent high SIAH expression in residual disease post-NACT/NST developed early relapse and succumbed to their chemoresistant and metastatic diseases (examples: patients #109 and #129). Conclusion: We propose that persistent high SIAH expression in residual tumors is associated with early tumor relapse and poor prognosis, while no or low SIAH expression in residual tumors is associated with tumor remission and good prognosis post-NACT/NST. SIAH: Human homologs of Drosophila Seven In Absentia (SINA); Pir: pathologic incomplete response; NACT: neoadjuvant chemotherapy; NST: neoadjuvant systemic therapy; PCR: athologic complete response.