Current Trends in Liquid Biopsy Tracking Resistance in Molecular Breast Cancer-Targeted Therapies

Sep 23, 2026

Uploaded by Jacob

Breast cancer remains a leading cause of cancer mortality worldwide, and evolving treatments require more accurate yet less invasive tools to monitor disease behavior. Liquid biopsy enables detection of small quantities of nucleic acids and cell-free DNA in patient blood, addressing limitations of needle biopsy by reducing invasiveness, reflecting tumor heterogeneity, and indicating molecular evolution toward metastasis. This review summarizes recent liquid-biopsy progress in breast cancer and evaluates key advantages and challenges.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Breast cancer burden and subtypes

Therapeutic background and resistance needs

Liquid biopsy for monitoring and biomarkers

ctDNA and tumor heterogeneity

Immunotherapy biomarkers such as PD-L1

Resistance mechanisms to breast cancer therapies

Drug degradation and receptor changes

Review Current Trends in Liquid Biopsy Tracking Resistance in Molecular Breast Cancer-Targeted Therapies Richard Tancredi 1, Navid Sobhani 2, Martina Catalano 3, Giandomenico Roviello 3, * and Daniele Generali 4 Academic Editor: Yutaka Suzuki Received: 17 February 2025 Revised: 25 March 2025 Accepted: 27 March 2025 Published: 9 April 2025 Citation: Tancredi, R.; Sobhani, N.; Catalano, M.; Roviello, G.; Generali, D. Current Trends in Liquid Biopsy Tracking Resistance in Molecular Breast Cancer-Targeted Therapies. Genes 2025, 16, 443 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)genes16040443 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Multidisciplinary Unit of Breast Pathology and Translational Research, Cremona Hospital, 26100 Cremona, Italy; [rictanc@hotmail.com](rictanc@hotmail.com) 2 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [navid.sobhani@cantab.net](navid.sobhani@cantab.net) 3 Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, 50139 Florence, Italy; [martina.catalano@unifi.it](martina.catalano@unifi.it) 4 Department of Medicine, Surgery and Health Sciences, University of Trieste, 34100 Trieste, Italy; dgenerali@units.it * [Correspondence: giandomenico.roviello@unifi.it](Correspondence: giandomenico.roviello@unifi.it) Abstract: Breast cancer (BC) is the most commonly occurring type of cancer in women, being a major cancer-related cause of mortality worldwide. With the advancement in current therapeutic options, including hormone therapy and targeted therapies, there is a need for more accurate and less invasive options to monitor cancer progression in patients. Liquid biopsy has evolved rapidly, being able to detect small quantities of nucleic acids or cell-free DNA in the blood of BC patients. This method addresses three major issues of needle biopsy: firstly, it is more permissive by being less invasive and does not require needling the organs; secondly, it covers for the heterogeneous nature of the tumor of origin, which could lead to an otherwise inaccurate representation of the cancer-driving mutations; thirdly, it better represents the type of tumor that the primary tumor is going to evolve into before it starts to metastasize. This current review will address the current advancementsin liquid biopsy in the context of BC, highlighting the pros and challenges. Keywords: liquid biopsy; ctDNA; CTC; biomarkers; breast cancer 1. Introduction Almost 12% of the cancers that occur in women worldwide are breast cancer (BC), making it second only to lung cancer in incidence [1] . In 2022, 665,684 women died of BC, which ranks fourth in cancer mortality around the globe [2] . Based on different receptor expressions, BC can be divided into four different subtypes: two luminal subtypes (luminal A and luminal B), the human epidermal growth factor receptor 2 (HER2) subtype, and triplenegative BC (TNBC), which does not express any of these three receptors [3] . Overall, ERpositive and progesterone receptor (PR)-positive breast cancer are called hormone receptorpositive (HR-positive) cancers, which make up 70% of all breast cancer malignancies [3] . Briefly, in hormone receptor-positive (HR+) BC, endocrine therapy (ET) is the base of the first-line therapy. HER2+ patients are treated by adjuvant antibody trastuzumab-based therapy, targeting the HER2 receptor [4] . Antibodies conjugated with chemotherapies targeting HER2+ BC cells have been successfully tested. However, in TNBC where there are no receptors to target, alternative therapies are most needed [

FAQs

Why is liquid biopsy considered a better option than needle biopsy for breast cancer monitoring?

Liquid biopsy is less invasive and does not require organ puncture. It also captures tumor heterogeneity and can reflect molecular changes before metastasis, improving representativeness compared with sampling a single tumor site.

How does liquid biopsy help with therapy resistance in molecular breast cancer?

By measuring circulating components such as ctDNA and detecting relevant biomarkers, it can support earlier identification of patients who may relapse or develop resistance. The review emphasizes the need for timely diagnostic methods linked to resistance mechanisms.

Which biomarkers and sample types are discussed in the context of liquid biopsy?

The document highlights nucleic acids/cell-free DNA detection and immunotherapy-related biomarkers, especially PD-L1. It also mentions detection across CTCs, exosomes, plasma, and PBMCs, alongside studies evaluating PD-L1 expression in these sources.

Sep 23, 2026

Uploaded by Jacob