Measuring Breast Tumor DNA in Blood Can Keep Disease in Check Longer
People with a specific breast cancer subtype whose therapy was changed based on results of a liquid biopsy had significantly longer time to disease progression in a clinical trial.
The pay is low and the work is spotty at the best of times, but one of the more rewarding aspects of being a freelance medical journalist is that you get to see promising new techniques and treatments develop over time, growing from a faint blip on the medical research radar screen, to a promising candidate in clinical trials, to a blockbuster, practice-changing therapy.
For example, at the American Society of Hematology annual meeting in 2011, I first learned about PCI-32765, a drug that didn’t yet have a name but was already wowing researchers with its effectiveness against two hematologic malignancies, a.k.a “blood cancers”: chronic lymphocytic leukemia and mantle cell lymphoma.
Today that drug, with the generic name ibrutinib and marketed under the tradename Imbruvica, is an important component of first-line therapy for both diseases, and is also approved for the treatment of other rare, aggressive cancers.
Similarly, I first heard about circulating tumor DNA (ctDNA), also called “liquid biopsy,” at a gastroenterology conference in 2015. At the time, the technique, which involves detection of bits of DNA that have sloughed off from tumors and can be isolated from circulating blood, was considered a promising research tool and possible diagnostic aid, but whether it would have practical clinical applications was still unknown.
Ten years later, ctDNA has clearly come into its own, as both a tool for predicting disease prognosis, and as a marker to tell clinicians that a change in treatment may be needed.
Breast Cancer Breakthrough
As I reported for Oncology News Central from the 2025 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, researchers in the SERENA-6 trial found that they could use ctDNA to monitor for early signs of a drug-resistance mutation in the blood of people being treated for one type of breast cancer, and if the mutation was detected, they could swap out one drug and replace it with another, more powerful drug, allowing people to remain on their first line of therapy longer and have a better quality of life than those who remained on their original drug regimen.
The trial involved people with a subtype of breast cancer called hormone receptor-positive, HER2-negative (HR+/HER2-) disease. These tumors are susceptible to treatment with drugs that block hormonal activity, but lack receptors for another target, HER2, that would otherwise respond to drugs such as trastuzumab (Herceptin).
People with this type of tumor typically receive as first-line therapy a combination of a hormone-blocking drug called an aromatase inhibitor, and a second drug targeted toward cyclin-dependent kinases 4 and 6 (CDK4/6), two enzymes (proteins) that are involved in cancer cell division and replication. This combination can be highly effective at keeping cancer at bay for many months or years.
But cancer cells are highly adaptable to stresses such as being targeted by effective treatment, and can rapidly evolve to avoid destruction. So people with HR+/HER2- breast cancers who are treated with a combination of an aromatase inhibitor and CDK4/6 inhibitor often develop a mutation in the estrogen-receptor gene ESR1, which can cause tumors to become resistant to therapy. When this happens, they may have to be switched to a second line of treatment, such as chemotherapy, with worse outcomes and shorter disease-free intervals than with first-line therapy.
But as Nicholas Turner, MD, PhD, from the Royal Marsden Hospital in London, UK, and colleagues reported at ASCO 2025, people with HR+/HER2- breast cancers who were monitored with ctDNA for early signs of an ESR1 mutation and then had the aromatase inhibitor swapped out and replaced with a more potent type of hormone blocker known as a selective estrogen receptor degrader (SERD) had a nearly 7-month longer time until their disease began to get worse, and a 16-month longer preservation of their quality of life than those who continued on the aromatase inhibitor and CDK4/6 inhibitor combination.
As ASCO breast cancer expert Eleonora Teplinsky, MD, from Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said at a press conference during ASCO 2025, ctDNA can reveal the presence of a mutation many weeks or months before evidence of drug resistance shows up on imaging scans, and “when patients progress on scans, we’re already behind. We’re switching therapy and we’ve already lost control in some sense. What this study does is an early-switch approach, before we see disease progression on imaging, allowing us to essentially stay ahead of the curve.”
The SERENA-6 trial was funded by AstraZeneca.
Turner disclosed a consulting or advisory role for AstraZeneca, Exact Sciences, Gilead Sciences, GlaxoSmithKline, Guardant Health, Inivata, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Relay Therapeutics, Repare Therapeutics, and Roche.
Teplinsky disclosed honoraria from Sermon and a consulting or advisory role for Novartis, Daiichi Sankyo/AstraZeneca, Pfizer, Immunogen, Novartis, and AbbVie.
Neil Osterweil is an award-winning medical journalist with more than 40 years of experience reporting on medicine and health care.