Breast cancer: further evidence supporting the clinical use of circulating biomarkers

This year, at the very moment when the European regulatory authorities have just recommended the approval of the therapeutic strategy for SERENA-6, an update of the more mature and still positive results of the study is presented in an oral session by Professor Francois-Clement Bidard, medical oncologist at Institut Curie and Professor at the University of Versailles-Saint-Quentin-en-Yvelines. These works, which are part of the framework of the IHU Institute for Women's Cancers, will be the subject of a forthcoming publication in The Lancet Oncology. 

"Ten years after the conception of our pioneering PADA-1 trial, the results of SERENA-6 presented today at ASCO confirm the lasting benefit of our original approach aimed at monitoring circulating tumor DNA to detect early a mechanism of resistance to hormone-dependent metastatic breast cancer treatments and adapt treatments accordingly ," states Professor Francois-Clement Bidard, Director of the Clinical Investigation Center of Institut Curie (Inserm CIC-2501) "Changing therapy on the basis of a blood-based signal and while patients do not show any clinical signs of cancer re-evolution, constitutes a real paradigm shift towards adaptive oncology to significantly improve the management and quality of life of patients".
 

The vast majority of metastatic breast cancers are hormone-dependent: the tumor cells, via the estrogen receptors present on their surface, capture the hormones which then stimulate the expansion of the cancer. The standard of treatment for this type of breast cancer most often consists of hormone therapy combining an aromatase inhibitor drug (decreasing the production of estrogens) with a cell proliferation inhibitor (CDK4/6 inhibitor). However, for almost 40% of patients, mutations occur at the gene level ESR1 (coding for the estrogen receptor), leading to resistance to aromatase inhibitors, and ultimately, to a re-evolution of the cancer that has become resistant. 

These ESR1 mutations can most often be detected in the blood several months before they lead to a re-evolution of the cancer. Therefore, the premise of the work of the Institut Curie teams is that the use of circulating tumor DNA opens a "window of opportunity" to target these resistance mutations and change treatment.
 

SERENA-6: A Novel Therapeutic Strategy at the Heart of Adaptive Oncology

Designed on the basis of the concept and the results of the PADA-1 academic study carried out by Professor Francois-Clement Bidard at Institut Curie and promoted by the Unicancer Group in France, SERENA-6 is a global phase 3 double-blind trial led by AstraZeneca and conducted in nearly 3,000 women with hormone-dependent metastatic breast cancer. In this unprecedented study, as soon as the ESR1 mutation was detected in the patients' blood - while they showed no signs of their disease progressing – the researchers tested a change in oral hormone therapy (with Camizestrant, developed by the AstraZeneca laboratory). The very first results of SERENA-6, reported last year, demonstrated the effectiveness of Camizestrant and its very good tolerability. 

A Lasting Clinical Benefit of Therapeutic Adaptation Guided by Circulating Tumor DNA Detection

Additional results are reported at the ASCO 2026 congress, confirming the first results reported in 2025. Indeed, the data collected confirm the main benefit of progression-free survival on a longer follow-up of patients who received Camizestrant, with a median improvement in progression-free survival of 7.6 months. Almost 35% of patients did not have a re-evolution of the disease two years after the change of treatment. 

Another key secondary evaluation criterion: progression-free survival-2 (PTSD2) which makes it possible to evaluate the effect of a treatment over a longer time. The SSP2 is the time until the second re-evolution of the cancer, and makes it possible to estimate if the benefit acquired with the change of treatment is preserved during the history of the disease. In SERENA-6, this PFS2 is statistically significant with a median improvement of 6.6 months, reassuring data on the sustainability of the benefit. Moreover, the first data on overall survival, although preliminary, shows a positive trend. Finally, and in accordance with the previous results, the overall tolerance is good and no new significant toxicity signals have been observed.

Green light from the European Medicines Agency (CHMP)

"These results were highly anticipated due to the novelty of this approach, SERENA-6 being the first adaptive oncology trial conducted by the pharmaceutical industry and taking up the concept initially explored in PADA-1 to register a new drug. The consolidated results presented today argue in favor of adopting this strategy based on circulating tumor DNA. With the recent green light from the scientific committee of the European Medicines Agency (EMA), and subject to the upcoming discussions at the French level, we are getting even closer to possible routine use", declares Professor Francois-Clement Bidard. "PADA-1 and SERENA-6 are a notable turning point, opening great prospects for changing the way that we treat cancers ".

 

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