DNA methylation in breast cancer - early detection and biomarker discovery through current and emerging approaches

Sep 23, 2026

Uploaded by Jake

Breast cancer remains one of the most common cancers in women worldwide, and early detection is crucial for improving outcomes. This review addresses limitations of current screening and highlights liquid biopsy as a non-invasive strategy. It focuses on DNA methylation, an epigenetic change that often occurs before genetic alterations, enabling biomarker development. The work surveys advances in methylation detection, biomarker discovery from single-omics and multi-omics studies, and machine-learning methods. It also discusses remaining challenges and future directions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

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Abstract

Background

Breast cancer screening limitations

DNA methylation as an epigenetic biomarker

Liquid biopsy for biomarker detection

Hum and Lee Journal of Translational Medicine (2025) 23:465 [https://doi.org/10.1186/s12967-025-06495-2](https://doi.org/10.1186/s12967-025-06495-2) Journal of Translational Medicine REVIEW Open Access DNA methylation in breast cancer: early detection and biomarker discovery through current and emerging approaches Melissa Hum 1 and Ann S. G. Lee 1,2,3* Abstract Breast cancer remains one of the most common cancers in women worldwide. Early detection is critical for improving patient outcomes, yet current screening methods have limitations. Therefore, there is a pressing need for more sensitive and specific approaches to detect breast cancer in its earliest stages. Liquid biopsy has emerged as a promising non-invasive method for early cancer detection and management. DNA methylation, an epigenetic alteration that often precedes genetic changes, has been observed in precancerous or early cancer stages, making it a valuable biomarker. This review explores the role of DNA methylation in breast cancer and its potential for developing bloodbased tests. We discuss advancements in DNA methylation detection methods, recent discoveries of potential DNA methylation biomarkers from both single-omics and multi-omics integration studies, and the role of machine learning in enhancing diagnostic accuracy. Challenges and future directions are also addressed. Although challenges remain, advances in multi-omics integration and machine learning continue to enhance the clinical potential of methylation-based biomarkers. Ongoing research is crucial to further refine these approaches and improve early detection and patient outcomes. Keywords Breast cancer, DNA methylation, Liquid biopsy, Early detection, Biomarker, Multi-omics, Machine learning Background Breast cancer is the most commonly diagnosed malignancy among women and remains a leading cause of cancer-related mortality. Early detection is crucial for improving treatment outcomes and survival rates. While mammography remains the gold standard for breast cancer screening, its sensitivity is reduced in women with *Correspondence: Ann S. G. Lee [dmslsg@nccs.com.sg](dmslsg@nccs.com.sg) 1 Division of Cellular and Molecular Research, National Cancer Centre Singapore, 30 Hospital Boulevard, Singapore 168583, Republic of Singapore 2 SingHealth Duke-NUS Oncology Academic Clinical Programme (ONCOACP), Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore 3 Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, Singapore 117593, Singapore dense breast tissue, increasing the risk of missed diagnoses [1]. Additionally, mammography can lead to false positives and overdiagnosis, resulting in unnecessary biopsies and overtreatment [2]. These limitations underscore the need for highly sensitive and specific biomark ers to improve early detection and risk assessment. DNA methylation, a key epigenetic modification, regulates gene expression without altering the DNA sequence and is essential for normal cellular function. However, aberrant DNA methylation plays a pivotal role in cancer development. In breast cancer, hypermethylation of tumor suppressor genes (e.g. BRCA1, ITHI5, RASSF1 A) and global hypomethylation contribute to disease development and progression [3–5]. Methylation changes often arise early in tumorigenesis, preceding genetic mutations, making them an attractive biomarker for early detection [6, 7]. Unlike the heterogeneity of gene © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission unde

FAQs

Why is early detection important in breast cancer?

Early detection improves treatment outcomes and survival. Current screening methods have limitations that can miss cancers at the earliest stages.

How does DNA methylation support breast cancer biomarker development?

DNA methylation regulates gene expression without changing the DNA sequence, and aberrant methylation is involved in cancer development. Methylation changes can occur early, making them useful biomarkers for detection.

What role does liquid biopsy play in this research area?

Liquid biopsy offers a minimally invasive, repeatable way to detect tumor-derived signals in blood or plasma. It enables detection of methylation patterns related to ctDNA and can support early detection and monitoring.

Sep 23, 2026

Uploaded by Jake