Health. Metastatic Breast Cancer: A Promising New Treatment

Hormone-dependent breast cancer is the most common breast cancer – accounting for 80% of diagnosed breast cancers. It also has the best prognosis.

However, at themetastatic stage – when cancer cells have migrated far from the initial cancer area – it becomes resistant to standard treatment, a hormone therapy that blocks the activation of the estrogen receptor while inhibiting cell proliferation.

This resistance occurs in nearly 40% of cases. It is most often explained by mutations in the estrogen receptor gene ESR1 that lead to resistance to hormone therapy.

Liquid biopsy to identify resistance mutations early

These mutations can be detected months before cancer reactivation using a liquid biopsy; a blood test that identifies circulating tumor DNA. Detecting it early would then make it possible to target the mutations responsible for resistance using SERD, a family of hormone therapy molecules, selective estrogen receptor inhibitors. This family has recently been enriched with new, more effective molecules, including camizestrant (AstraZeneca).

A large international phase 3 clinical trial, the results of which were presented on Sunday, June ^1, at the American Society of Clinical Oncology (ASCO) and published in The New England Journal of Medicine , monitored 3,000 patients with hormone-dependent metastatic breast cancer. All were receiving standard treatment and had blood tests every two to three months to detect a resistant mutation.

The 315 patients who had this mutation were divided into two groups: the first continued to receive standard treatment, the second received camizestrant combined with the cell proliferation inhibitor. Oral hormone therapy was changed at the first signs of genetic mutations in the blood.

"Patients receiving camizestrant saw their risk of cancer progression reduced by 56%, delaying the time to first re-evolution by approximately 6 months on average. At 12 months, the progression-free survival rate was 60.7% for patients who received camizestrant compared to 33.4% for those who did not. At 24 months, progression-free survival reached 29.7% compared to 5.4%," the Institut Curie describes in a press release.

Another advantage was that quality of life was also improved: patients on standard treatment saw their quality of life decline as early as 6 months after the appearance of the mutations, compared to an average of 23 months for patients who changed treatment.

A strategy applied to other cancers?

"Ten years will have passed between the development in the laboratory of a blood test detecting resistance mutations and the results of the SERENA-6 study. If the PADA-1 study, which we conducted in France thanks to the Unicancer network, had established proof of concept, SERENA-6 sets in stone that our strategy of intercepting resistance, thanks to regular non-invasive monitoring by blood tests and a change of treatment, leads to a tangible benefit for the survival and quality of life of patients," enthuses Professor François-Clément Bidard, medical oncologist at the IHU Women's Cancer Institute of the Institut Curie, Professor at the University of Versailles-Saint-Quentin and co-pilot of the SERENA-6 study.

"These very positive results validate the potential of our interception approach by detecting mutations in circulating tumor DNA. The research and clinical prospects are now fascinating, as this strategy could potentially be extrapolated to other situations and types of cancer, and lead to the registration of new drugs."