Presentations

Abstract

Introduction:

While high-resolution imaging and advancements in therapies have significantly improved breast cancer survival rates, 43,170 breast cancer patients will die in the United States in 2023 alone. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and disproportionately affects BRCA1 mutation carriers and young black women. Black/African American (AA) patients have the highest mortality and the shortest survival of any racial/ethnic group in the US. Persistent cancer racial disparity remains due to a variety of risk factors. Genetics, structural racism, medical mistrust, treatment disparity, unstable employment, limited access to quality healthcare, and poor education background all contribute to cancer racial disparity and high mortality detected in many underserved communities. The SEER/CDC data show an 8% lower breast cancer incidence rate but a 41% higher mortality rate in Black/AA patients when compared to their white counterparts.

Methods:

Chart review was conducted using Sentara MD Office/EPIC and VOA iKnowMedicine portals to update tumor relapse, metastasis, and survival information in 577 TNBC patients. Supported by strong evidence in developmental, evolutionary, and cancer biology, we hypothesize that persistent EGFR-K-RAS-SIAH pathway activation is a major driving force of TNBC malignancy, racial disparity, early relapse, and high mortality. We propose to integrate SIAH expression to augment the existing clinicopathological parameters to improve patient risk stratification, therapy quantification, and relapse/survival prediction at the 1st-line neoadjuvant settings.

Results:

We report that cancer disparity and high mortality rates are even more pronounced in our racially-diverse communities in Hampton Roads Virginia. We discovered that SIAH is a tumor-specific, therapy-responsive, and prognostic biomarker whose SIAHHigh/Low expression can be used for patient risk stratification, cancer racial disparity detection, and relapse/survival prediction in TNBC. High SIAH expression in residual tumors reflects tumor-driving EGFR/K-RAS/SIAH pathway activation (ON) that will predict cancer disparity, treatment resistance, early relapse, and poor survival. Low SIAH expression in residual tumors reflect effective treatment and EGFR/K-RAS/SIAH pathway inactivation (OFF) that will predict tumor remission and prolonged survival.

Conclusion:

We detect a major cancer racial disparity of Black/White TNBC patients at Sentara- EVMS-VOA. Our local Black/AA TNBC patients have a 1.6-fold higher mortality rate than their white counterparts. Encouraged by our preliminary data, we aim to develop a SIAH-centered biomarker panel by measuring the EGFR/RAS/SIAH pathway activation (ON)/inactivation (OFF), and use SIAH as a new prognostic biomarker to risk stratify patients, detect cancer racial disparities, forecast tumor relapse, and predict patient survival at 1st-line neoadjuvant settings. By focusing on EGFR/RAS/SIAH pathway, we will be able to detect racial disparity, reduce TNBC mortality rate, and identify and tailor therapies to save more patients from TNBC.