Abstract 5315: Identification of urinary proteome signatures associated with triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype, accounts for ~15% of all breast cancers and is associated with a poor prognosis and high rates of recurrence and distant metastases. Patients diagnosed with TNBC have limited treatment options and are often restricted to chemotherapy-based regimens, in stark contrast to patients with other breast cancer subtypes where the development of targeted therapeutics have significantly improved patient outcomes. TNBC is characterized by the loss of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. This and the genetic and molecular tumor heterogeneity of TNBC has not only limited advances in the development of targeted therapy but also in the identification of biomarkers that can predict disease status and monitor treatment response. Advances in next-generation sequencing technologies have led to the identification of promising clinically actionable mutations however these tests often require invasive procedures to obtain tumor tissue and lack the ability to monitor treatment efficacy or detect recurrence, highlighting the need for non-invasive markers. A number of serum protein biomarkers have been evaluated in TNBC however none have yet to be successfully deployed in the clinic as indicators of disease. We have previously established that the urinary proteome can serve as a source of highly specific and sensitive biomarkers that can detect disease status and stage of multiple cancer types. Within the context of our global proteomics approach to cancer biomarker discovery, we have utilized the SomaScan discovery platform to identify 281 proteins that are differentially expressed in the urine of patients with TNBC compared to the urine of age- and sex-matched controls. The gene expression profiles of these proteins in TNBC tumor tissue were compared to those of normal breast tissue utilizing the R2 Genomics Platform. Proteins whose gene expression profile was consistent with the proteomic data were validated for the ability to distinguish between TNBC and non-TNBC diagnoses using mono-specific ELISAs of patient urine samples. These results demonstrate that a global proteomics approach coupled with clinical gene expression data can be effectively utilized to identify potential biomarkers for TNBC. These findings identify clinically relevant proteins that should be further explored as potential biomarkers in the development of non-invasive diagnostics for TNBC. (This work was supported by the Breast Cancer Research Foundation and the Nile Albright Research Foundation). Citation Format: Michael N. Lombardo, Roopali Roy, Susan Pories, Meg Lotz, Rama Aldakhlallah, Simon T. Dillon, Towia A. Libermann, Marsha A. Moses. Identification of urinary proteome signatures associated with triple-negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5315.