ctDNA-guided monitoring and ESR1 resistance in breast cancer
Dr. Basma M’Barek (FV Hospital, Vietnam) approached precision oncology from a longitudinal perspective, discussing how circulating tumor DNA (ctDNA) can guide not only initial treatment decisions but also continuous monitoring in breast cancer. She emphasized tumor heterogeneity and importance of capturing clonal diversity throughout the disease course. As she explained, “ctDNA is shredded DNA from all the clones of the tumor in our body, offering a more comprehensive view than single-site biopsy alone.” This is particularly relevant in breast cancer, where evolving clones drive treatment response and resistance, making ctDNA a dynamic and repeatable tool to track the disease over time.
Early “truncal” mutations like PIK3CA differ from later, therapy-induced mutations such as ESR1. Because ESR1 mutations may be missed by tissue biopsy due to spatial heterogeneity, liquid biopsy offers a key advantage by capturing signals from all disease sites. As she noted “With sensitive assays, including those used in platforms like Gene Solutions, clinicians can reliably detect ESR1 mutations in plasma, enabling earlier and more targeted intervention.”
She shared her treatment experience based on data from the PADA-1 study: “We should try to detect the ESR1 mutation starting from 6 months after initiation of first-line aromatase inhibitor plus CDK4/6 inhibitor therapy and continue monitoring regularly every 3 months to identify resistance before clinical progression becomes visible.” These molecular changes can precede imaging findings by six to nine months, allowing earlier action. Through both trial data and a clinical case, she showed how ctDNA and MRD status—both their presence and absence—can shape treatment decisions, from early switching at molecular resistance to supporting more aggressive treatment when ctDNA is not detected.
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