How can we detect the escape of a tumor (in this case, metastatic hormone-dependent breast cancers) as early as possible by detecting the appearance of new mutations? By regularly measuring circulating tumor DNA (ctDNA) with a simple blood test. This is the concept born at the Curie Institute several years ago and which has just seen its culmination presented in a plenary session (a very important distinction among more than 5,000 presentations) at the 61e 2025 edition of the International Cancer Congress (ASCO), which brings together nearly 40,000 international specialists from May 30 to June 4 in Chicago (United States).
This work, the essay Serena- 6, undoubtedly marks an important step in the management of breast tumors. This is the first global phase 3 trial to use a ctDNA-guided approach to detect the emergence of tumor resistance to treatment. In this type of most frequent breast cancer (65%), called hormone-dependent metastatic, »less than 5% of women have an estrogen receptor (ESR1) mutation before starting treatment,” explains Professor François-Clément Bidard, medical oncologist at the Curie Institute (Paris) and co-pilot of this global work. On the other hand, when the disease progresses, we know that this mutation is then found in 40% women..
Informing the decision to change treatment earlier
Hence the idea of identifying the moment of their appearance as early as possible. Because this mutation is detectable in the blood by a simple blood test, detecting the DNA released by the tumor cells. But be careful, at this stage of research, this technique is not yet usable on a diagnostic level but is used strictly to monitor treatment failure.
François-Clément Bidard, who has been working on the subject for a long time in collaboration with the Unicancer network, had already reported this approach in 2022 in an academic essay called PADA -1. He then demonstrated that blood tests carried out every two months made it possible to detect the mutation before it manifested itself radiologically as an increase in the size of the tumor, which, precisely because of this mutation, then became insensitive to treatment, a bit like the phenomenon of antibiotic resistance developed by bacteria.
This is where close biological monitoring goes beyond that provided by imaging, by making it possible to inform the decision to change treatment earlier, before the progression of the disease is visible on scans, carried out approximately every 3 to 4 months.
A simpler and also less expensive solution. However, since the presentation of this concept, the AstraZeneca laboratory has proposed applying it to its new hormone therapy against breast cancer, camizestrant, a molecule from a new class of hormone therapy called SERDs.
And in the trial presented this year at Asco, two groups of about 150 women carrying the ESR1 mutation and receiving the standard treatment, an anti-aromatase combined with a CDK4/6 cell proliferation inhibitor, were followed with blood samples every 2 to 3 months. While the standard group continued the same treatment without modification, the experimental group had its hormone therapy modified and received the new SERD.
Biology here goes beyond radiology
Beyond the good tolerance of the treatment, the trial demonstrates that for women in the experimental group the risk of tumor progression decreased by 56%, their rate of survival without tumor progression at 12 months reaching 60.7 % compared to 33.4 % for the standard group.Moreover, oHere, we delay the progression of the tumor while preserving the quality of life of women.”, insists the specialist. Indeed, the analysis of the patients' questionnaires showed that this quality of life declined approximately twenty-three months after the change in treatment compared to six months for those who remained on standard treatment despite the presence of the mutation.
Good news: " These PCR techniques are not elitist are simple and above all already accessible in practice, the molecular biology platforms existing either internally in the most important anticancer centers, or externally for the others, specifies the oncologist. However, the question of their reimbursement will still need to be resolved, especially since the volume of tests carried out is set to increase rapidly."
A paradigm shift is therefore coming in monitoring the development of breast cancer, with biology here going beyond radiology. Monitoring by blood test approximately every 4 months should ultimately be suitable, estimates the oncologist, for around several thousand new patients per year in France.
There is no doubt that, very quickly, this biological monitoring will benefit other cancers besides breast cancer. Gaining time against cancer, regardless of its location, is a constant battle.
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