ICR researchers reveal how advanced breast cancers become resistant to hormone therapy

Researchers from the Institute of Cancer Research (ICR) have revealed why some advanced oestrogen receptor (ER)-positive breast cancers become resistant to hormone therapy.

The study used blood samples from the plasmaMATCH clinical trial to analyse traces of cancer DNA in the blood.

Secondary breast cancer, which occurs when cancer in the breast has spread to another part of the body, is estimated to affect 61,000 people in the UK.

Experts from the ICR’s Breast Cancer Now Toby Robins Research Centre analysed the blood samples to identify genetic mutations in the circulating tumour DNA of advanced ER-positive breast cancer patients and observed how they responded to fulvestrant.

The widely used hormone therapy, fulvestrant, is usually given to people with ER-positive breast cancer as either a first-line treatment or once other drugs have stopped working.

However, in some cases, patients’ cancer will often progressively develop resistance to the treatment.

The team found that 4% of ER-positive breast cancer patients with mutations in F404, combined with specific pre-existing mutations, caused overt resistance to fulvestrant hormone therapy.

These new mutations only occurred in patients with already-existing mutations in ESR1 prior to treatment.

Researchers confirmed that the combined effect of these pre-existing and new mutations created profound resistance to hormone therapy.

The study then tested four hormone therapies currently in clinical development and found that cells that have F404 mutations were sensitive to all of them.

Following approval of these therapies, patients who are likely to develop resistance to fulvestrant could be identified with a blood test and offered new, alternative treatments.

Dr Kotryna Temicinaite, head of research communication and engagement, Breast Cancer Now, said: “These findings help us understand how secondary breast cancer can become resistant to hormone therapies… and [identify which] other treatments we could use in the future if this resistance happens.”

Nicholas Turner, professor of molecular oncology at the ICR and consultant medical oncology at the Royal Marsden NHS Foundation Trust, said: “This could revolutionise the way we treat breast cancer by making use of these simple blood tests to match patients to alternative treatments, bringing them the best possible outcome.”