Major advanced breast cancer breakthrough discovered by Malaga oncologist and international team of researchers

An international team of researchers, including the medical oncologist at the Hospital Universitario Virgen de la Victoria and IBIMA Plataforma Bionand, Javier Pascual, has achieved very promising results that could help to change the treatment of advanced breast cancer and therefore, mark a milestone in the medical fight against this disease.

The results of the Serena-6 phase III clinical trial were released on Tuesday 1 July, showing that early switching to a new generation drug called camizestrant can double the time it takes to control the disease in some patients compared to standard, conventional hormone therapy. The switch is made possible only by a blood test and a new drug.

By detecting tumour resistance to treatment with a blood test before tumour growth has occurred using imaging techniques, it is possible to switch from the usual hormone treatment to the drug camizestrant and extend the period during which the cancer does not progress from nine to sixteen months.

The results have been published in the New England Journal of Medicine and were presented at the annual meeting of the American Society of Clinical Oncology (ASCO 2025).

In Malaga, according to the Spanish Association Against Cancer (AECC), 1,283 cases of breast cancer were detected in 2024 compared to 1,258 in 2023, which indicates that the disease continues to grow in the province.

In many patients with advanced "ER-positive/HER2-negative" breast cancer (i.e. tumours that grow because of hormones and not because of the HER2 protein), the usual treatment results from combining an aromatase inhibitor (reduces oestrogen production) with a drug that slows down cell division (CDK4/6 inhibitor). The hormone treatment, it is called, works well at first, but in four out of six cases the tumour learns how to evade the lack of hormones thanks to mutations in a gene called ESR1. When this happens, the drugs stop working and the cancer grows.

The idea of the study is both simple and revolutionary: to detect these resistance mutations before the tumour grows with a CT or imaging scan. Every two to three months, patients' blood is analysed for circulating tumour DNA fragments (ctDNA). When a mutation in the gene is identified, instead of waiting for the cancer to progress, they immediately switch to the new drug, camizestrant, "a hormone treatment that directly targets the oestrogen receptor, destroying it completely and thus defeating the mutation".

The study involved 3,256 women with advanced breast cancer who had received standard hormone treatment for six months, 315 of whom developed mutations in the ESR1 gene, all of which were detected by DNA analysis of tumour DNA in their blood. A group of these, 157 in total, were started on camizestrant when the mutation was detected in the bloodstream, while another 158 continued with standard hormone therapy until tumour progression became visible on imaging. In the first group, the cancer did not progress for 16 months, while in the second, it was at a standstill for much less: 9.2 months. The new drug thus reduced the risk of the disease worsening or death in the follow-up period by 56%.

This means an increase in patients' quality of life. Those who received this drug took 23 months to notice a deterioration in their health, compared to 6.4 months for those on the previous therapy.

Javier Pascual pointed out that "by anticipating tumour progression through DNA analysis in blood, we achieve additional weeks or months of disease control and quality of life for patients. Camizestrant is the first hormone therapy capable of completely degrading the oestrogen receptor, even when it is mutated. Instead of waiting for the tumour to "show up" on a scan, we attack the cause of resistance directly.

This drug makes a difference because it works in a completely new way compared to standard treatments. While the latter block oestrogen production or prevent hormones from activating the receptor, camizestrant destroys the oestrogen receptor completely, so that neither its normal form nor its mutated version can fuel tumour growth, making it a key direct approach as it prevents cancer cells from finding an escape route when the receptor undergoes mutations that previously rendered therapy useless.

In addition, the way to know if the cancer is becoming resistant is simple and convenient thanks to blood tests every two to three months, setting off an early alarm that allows treatment to be changed before the tumour grows again in imaging tests, so oncology no longer relies exclusively on CT or MRI scans to know if the cancer is progressing. Finally, the side effects of the drug are milder, increasing quality of life.

The trial, in any form, further opens the door to precision medicine based on blood-detectable biomarkers, prolonging tumour control, improving quality of life and generating new horizons for medical cures in other tumours such as lung, prostate or ovarian, as these also have resistance mutations detectable in blood. This would represent a paradigm shift in the management of multiple types of cancer.

"This trial shows that we can get ahead of tumour progression by identifying mutations in blood. As a result, patients switch to a more effective drug just as their tumour starts to wake up, achieving weeks or months of additional control without major side effects. It's a step forward for precision medicine," concluded Pascual.

Researchers will now study the long-term impact of this strategy, as well as more frequent follow-up protocols to detect mutations even earlier. In addition, new trials will be designed to test whether other cancers respond in the same way to blood test-guided drug switching. If this is confirmed, said IBIMA, "we could be looking at a new standard of cancer care in which the biology of each patient sets the course of treatment".