Ground-breaking research showing how changes in and around a single gene could help forecast a woman’s risk of getting breast cancer and predict her resistance to breast cancer drugs was presented at the first UK Breast Cancer Research Symposium in London.

The Symposium, which is being held in London by the charity Breast Cancer Now in collaboration with world-renowned breast cancer experts, features two research papers examining the role of the ESR1 gene.

This gene provides the instructions for making oestrogen receptors – the molecules in cells that recognise the hormone oestrogen and that, in around 80% of breast cancers, allow oestrogen to drive the growth of breast cancer.

Changes in this gene could have many implications for women’s risk of developing breast cancer and how a cancer may react to treatment.

Delyth Morgan, chief executive of Breast Cancer Now, said “The first UK Breast Cancer Research Symposium is a chance for many of the world’s leading cancer researchers to come together and hear about the latest research not only from their own discipline, but from others as well. Both discoveries relating to the ESR1 gene show great potential to tailor treatment for patients and reveal more about the genetics of breast cancer risk. It is work such as this that will lead to steady improvement in the prevention, diagnosis and treatment of breast cancer in coming years.”

Scientists have suggested that if mutations in ESR1 were more commonly found in secondary (metastatic) breast cancers, they could be causing primary cancers to become resistant to anti-hormone treatment.

This is why a team from the University of Pittsburgh, led by Dr Steffi Oesterreich, used a highly sensitive new  technology (called digital droplet PCR) to look for relevant non-inherited mutations in the ESR1 gene.

They examined 122 samples from both primary breast tumours and secondary breast cancer which had spread to the brain, bone and bloodstream.

They were able to identify significantly more mutations in secondary samples compared to primary samples.

Firstly this proves that ESR1 mutations can be found using this innovative method.

Secondly, it suggests that primary breast cancers containing ESR1 mutations could be an early indication that a tumour has the potential to develop resistance to anti-hormone treatment e.g. tamoxifen or aromatase inhibitors.

This knowledge might help doctors to change a patient’s treatment and tackle resistance before the cancer becomes fully unresponsive to anti-hormone drugs. This is something that can now be tested in clinical trials.

Dr Oesterreich said "The ESR1 gene has a very important role in the process by which cancers spread from the breast to elsewhere in the body. Research on the way this gene mutates will help us to identify the cancers which will relapse, and also those which will not respond to our current treatment. It shows how, in the future, new extremely sensitive technologies could  give us an ever more detailed picture of what is going on inside a patient’s breast cancer and how the cancer is responding to treatment.”

In a larger international study, research led by Dr Alison Dunning at the Department of Oncology at the University of Cambridge searched for inherited genetic changes in almost 120,000 women.

The study identified five genetic changes which affect a woman’s risk of a developing particular types of breast cancer. 

All of the genetic changes are found near the ESR1 gene and are believed to change the amount of oestrogen receptors in a breast cell. 

They also control three other nearby genes, not previously known to be involved in breast cancer.

These findings increase our understanding around women’s risk of developing breast cancer, which type of cancer they may get and provide new targets for cancer prevention.

Dr Dunning said “All five of the genetic variants we have found near the ESR1 gene affect the levels of oestrogen receptors in breast cells. This seems to indicate that if there are too few or too many oestrogen receptors then the breast cells are more likely to become cancerous.”

Both sets of results were discussed at the first UK Breast Cancer Research Symposium. 

Source: Breast Cancer Now