Is ctDNA ready to outpace imaging in monitoring early and advanced breast cancer?

ABSTRACT

Introduction

Circulating tumor DNA (ctDNA) and radiological imaging are increasingly recognized as crucial elements in breast cancer management. While radiology remains the cornerstone for screening and monitoring, ctDNA holds distinctive advantages in anticipating diagnosis, recurrence, or progression, providing concurrent biological insights complementary to imaging results.

Areas covered

This review delves into the current evidence on the synergistic relationship between ctDNA and imaging in breast cancer. It presents data on the clinical validity and utility of ctDNA in both early and advanced settings, providing insights into emerging liquid biopsy techniques like epigenetics and fragmentomics. Simultaneously, it explores the present and future landscape of imaging methodologies, particularly focusing on radiomics.

Expert opinion

Numerous are the current technical, strategic, and economic challenges preventing the clinical integration of ctDNA analysis in the breast cancer monitoring. Understanding these complexities and devising targeted strategies is pivotal to effectively embedding this methodology into personalized patient care.

KEYWORDS:

• Breast cancer
• liquid biopsy
• ctDNA
• radiomics
• imaging

Article highlights

• Integration of ctDNA into the therapeutic algorithm of ABC is progressively crucial, guiding the choice of targeted therapies such as alpelisib, elacestrant, and capivasertib.

• Both in the neoadjuvant and adjuvant setting, ctDNA enables the monitoring of minimal residual disease through innovative tumor-informed and tumor-agnostic approaches

• Pharmacokinetics and pharmacodynamics analyses play a vital role in understanding the effectiveness and potential side effects of anti-tumor drugs, as demonstrated in complementary analyses alongside the PALOMA-1 and MONARCH 3 studies.

• Radiomics stands as a crucial tool within the decision-making algorithm for breast cancer, as already demonstrated in predicting sentinel lymph node metastasis and forecasting the risk of disease recurrence

• In the screening setting, integrate ctDNA detection rates with the BI-RADS score yielded an impressive positive predictive value of 92.45%. In monitoring patients at risk of hereditary mutations, alterations in BRCA1 with MAF > 32.4% and BRCA2 with MAF > 28.5% were identified as useful criteria for identifying germline BRCA1/2 mutations

Declaration of interest

L Cereser reports consulting or advisory roles from AstraZeneca; L Gerratana reports consulting or advisory roles from AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, Merck Sharp & Dohme, Menarini Stemline, AbbVie; Research Funding from Menarini Silicon Biosystems; Travel Expenses: Menarini Stemline; F Puglisi reports consulting or advisory roles from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris; Research grant/funding from AstraZeneca, Eisai, and Roche. The other authors have no 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.

Reviewer disclosures

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

Additional information

Funding

The manuscript was supported by the Ministry of Health Ricerca Finalizzata grant [Grant Number: RF-2016- 02362544] to FP; by the CRO Aviano 5 × 10002014, redditi 2013 Cancer Specific Intramural Grant to LG