Searching for DNA methylation in patients triple-negative breast cancer: a liquid biopsy approach

ABSTRACT

Introduction

Liquid biopsies are proving to have diagnostic and prognostic value in many different cancers, and in breast cancer they have the potential to improve outcomes by providing valuable information throughout a patient’s cancer journey. However, patients with triple negative breast cancer (TNBC) have received little benefit from such liquid biopsies due to underlying limitations in the discovery and utility of robust biomarkers. Here, we examine the development of DNA methylation-based liquid biopsy assays for breast cancer and how they pertain to TNBC.

Areas Covered

We conducted a systematic review of liquid biopsy assays for breast cancer and analyzed their relevance in TNBC. We show that the utility of DNA mutation-based assays is poor for TNBC due to the low mutational frequencies across the genome in this subtype. We offer a detailed review of mDETECT – a liquid biopsy specifically designed for assessing tumor burden in TNBC patients.

Expert Opinion

DNA methylation are foundational and robust events that occur in cancer evolution and may differentiate almost all forms of cancer, including TNBC. Longitudinal patient monitoring using DNA methylation-based liquid biopsies offers great potential for improving the detection and management of TNBC.

KEYWORDS:

• Breast cancer
• liquid biopsy
• DNA methylation
• triple negative breast cancer
• blood test
• treatment response
• treatment monitoring
• detection

Article highlights

• TNBC is a subtype of breast cancer that is particularly aggressive and lacks conventional targeted therapies. Clinical management of TNBC has remained stagnant.

• Liquid biopsies have the potential to better stratify and manage TNBC patients.

• Current mutation-based assays are effective in identifying some breast cancer patients but are not applicable to all TNBC patients due to the low mutational profile of TNBC breast cancer tumors

• Frequent DNA methylation events have been characterized in breast carcinogenesis and have been shown to have prognostic and predictive value.

• Most DNA methylation assays are geared toward multi-cancer early detection screening platforms and have been poorly defined in TNBC-specific tumors.

• mDETECT is a DNA methylation-based liquid biopsy designed specifically for TNBC patients for managing patient response to treatment.

Declaration of interest

Irsa Shoukat and Christopher Mueller are principles in a start-up company aimed at commercializing the mDETECT assay. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was supported by the Canadian Cancer Society, Grant # 703282