Unmet Clinical Need: Developing Prognostic Biomarkers and Precision Medicine to Forecast Early Tumor Relapse, Detect Chemo-Resistance and Improve Overall Survival in High-Risk Breast Cancer

Abstract

Chemo-resistant breast cancer is a major barrier to curative treatment for a significant number of women with breast cancer. Neoadjuvant chemotherapy (NACT) is standard first- line treatment for most women diagnosed with high-risk TNBC, HER2+, and locally advanced ER+ breast cancer. Current clinical prognostic tools evaluate four clinicopathological factors: Tumor size, LN status, pathological stage, and tumor molecular subtype. However, many similarly treated patients with identical residual cancer burden (RCB) following NACT experience distinctly different tumor relapse rates, clinical outcomes and survival. This problem is particularly apparent for incomplete responders with a high-risk RCB classification following NACT. Therefore, there is a pressing need to identify new prognostic and predictive biomarkers, and develop novel curative therapies to augment current standard of care (SOC) treatment regimens to save more lives. Here, we will discuss these unmet needs and clinical challenges that stand in the way of precision medicine and personalized cancer therapy.

Keywords: Chemo-resistant breast cancer; Clinicopathological predictors; High-risk breast cancer; Locally advanced breast cancer; Neoadjuvant chemotherapy; Relapsed and metastatic breast cancer; Therapy-responsive and prognostic biomarker for future clinical application; Tumor-driving RAS/SIAH/EGFR/ HER2 signaling pathways in breast cancer.

Figure 1:. SIAH is a binary, tumor-specific, therapy-responsive, and prognostic biomarker in breast cancer.

SIAH^ON/OFF expression in residual tumors can be used to stratify patients, identify good prognosis (SIAH expression is absent or low) or poor prognosis (SIAH expression is high), forecast early tumor relapse, predict patient survival with post-neoadjuvant chemotherapy (NACT).