Scientists have furthered our understanding of how some secondary breast cancers can become resistant to the hormone therapy fulvestrant.
Scientists have increased our understanding of how some secondary breast cancers can become resistant to the hormone therapy fulvestrant.
Scientists funded by Breast Cancer Now studied how oestrogen receptor (ER) positive secondary breast cancer can become resistant to fulvestrant.
Using samples from a clinical trial, they found that new changes in the oestrogen receptor gene ESR1 stopped fulvestrant from working.
The team at The Institute of Cancer Research, London, also found that some drugs that are currently in development showed promising results for treating fulvestrant-resistant cancer cells in the lab.
Fulvestrant resistance
Fulvestrant is a widely used type of hormone therapy that's usually given to people with ER-positive secondary breast cancer. But, breast cancer cells can become resistant to this treatment over time.
So, Professor Nicholas Turner at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR) wanted to better understand how this happens.
Looking for the mechanisms
Nicholas and his team studied blood samples donated by people taking part in the plasmaMATCH clinical trial. In this clinical trial, researchers are using blood tests, also called liquid biopsies, to look at small traces of cancer DNA in the blood.
For this study, the team looked at how people with changes in a gene called ESR1 responded to fulvestrant.
The team found that 4% of breast cancers developed new changes to the ESR1 gene when treated with fulvestrant, on top of existing changes. And that the combination of these gene changes made the cancer resistant to fulvestrant.
Understanding the ESR1 gene
To build on these findings, the researchers wanted to better understand how these gene changes contribute to drug resistance.
ER-positive breast cancers use oestrogen in the body to help them grow. So, hormone therapies like fulvestrant target a protein called the oestrogen receptor to stop this.
The ESR1 gene makes the oestrogen receptor proteins. Using computer modelling, the researchers found that ESR1 gene changes disrupted how fulvestrant targets these receptors, stopping the drug from working.
Searching for alternatives
Nicholas and his team then tested a series of hormone therapies currently in clinical development on fulvestrant-resistant cancer cells. And they found that these cancer cells were sensitive to all 4 therapies tested in the lab.
This opens new avenues for treatments that could treat secondary ER-positive breast cancers.
Our study makes use of innovative blood tests which detect genetic changes present in a patient’s cancer, without the need for any invasive procedures. The discovery of these specific genetic changes in estrogen receptor positive breast cancer helps to explain why some patients develop resistance to fulvestrant, and which treatments will be likely to work instead. This could revolutionise the way we treat breast cancer, by making use of these simple blood tests to match patients who may develop fulvestrant resistance to alternative treatments, bringing them the best possible outcome.
Professor Nicholas Turner
Professor of Molecular Oncology and Consultant Medical Oncologist
These findings help us understand how secondary breast cancer can become resistant to hormone therapies like fulvestrant and what other treatments we could use in the future, if this resistance happens. With an estimated 61,000 people living with secondary breast cancer in the UK, research like this is vital.
Dr Kotryna Temicinaite
Head of research, communication and engagement at Breast Cancer Now
This study was published in the journal of Cancer Discovery and funded by Breast Cancer Now, Cancer Research UK and National Institute for Health and Care Research.
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This study was published in the journal of Cancer Discovery and funded by Breast Cancer Now, Cancer Research UK and National Institute for Health and Care Research.