Researchers part-funded by Breast Cancer Now have identified changes in breast cancer cells that could in future help predict the likelihood of recurrence in patients taking a common type of hormone therapy known as aromatase inhibitors.

Oestrogen receptor positive (ER-positive) breast cancers in some cases may come back decades after treatment. Understanding early on if the cancer is developing resistance to treatment would bring significant benefit to women with ER-positive breast cancer.

In the study, researchers at the University of Edinburgh, analysed tumour samples from women treated with the drug letrozole. Women participating in the study didn’t undergo surgery to remove their tumours, meaning the scientists could track how breast cancer cells changed during treatment.

The researchers – led by Dr Andy Sims – analysed which genes are switched on and off in tumours that started growing again after initially shrinking in response to letrozole, and in those that didn’t. They found that the treatment almost immediately triggered changes in cancer cells, which became more pronounced over time.
Importantly, the team spotted subtle differences between the two types of tumours. They found specific chemical signatures – called epigenetic changes – that were absent in tumours that developed resistance but were present in tumours that had remained dormant and did not start growing again. These differences were present in the first weeks of treatment, suggesting it may be possible to predict which women are more likely to see their breast cancer return.

Dr Andy Sims, of the MRC Institute of Genetics and Molecular Medicine, said:

Treatment resistance is hard to study and laboratory experiments often do not closely resemble the situation in patients. This is the first time we have been able to investigate genetic changes in individual patients’ tumours over time. 

We hope the findings will help to develop new tests that predict which women on hormone therapy are likely to relapse so that they can be offered alternative treatments.

Dr Simon Vincent, Director of Research at Breast Cancer Now, said:

This is a promising early finding that could help us better understand how some breast cancers become resistant to therapy and what we can do about it. Drug resistance is a major hurdle that we must overcome if we are to finally stop women dying from breast cancer. It’s vital that we understand exactly how and when cancer cells begin to adapt to and resist treatment, so that we can remain one step ahead of the disease.

It’s really encouraging that this study has identified epigenetic changes that may help predict which patients are more likely to see their cancer come back. We hope further research will now help to identify exactly when these changes may begin to appear and find ways to target them, enabling us to intervene at the right time. 

Through research like this, we hope to one day be able to identify when therapies are becoming less effective and when a change of treatment might be appropriate.

The study was published in journal Breast Cancer Research, and was supported by Breast Cancer Now, the Marie Skłodowska-Curie Individual Fellowship and the Wellcome Trust Institutional Fund.