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Transforming treatment for the most common type of breast cancer

We played a leading role in clinical trials that demonstrated the effectiveness of aromatase inhibitors in breast cancer, and in identifying and validating biomarkers to determine who could benefit from these drugs. 

Breast cancer cell

Photo: Bruce Wetzel and Harry Schaefer, National Cancer Institute, National Institutes of Health

The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust played a leading role in the clinical development of a class of hormonal drugs called aromatase inhibitors that were effective in treating some breast cancers.

Aromatase inhibitors are an important part of hormone treatment for women with the most common type of breast cancer, which relies on the oestrogen receptor for its growth. These oestrogen receptor-positive breast cancers nowadays make up about 80% of cases.

These tumours need oestrogen to grow and survive, and researchers found that stopping women’s bodies from producing oestrogen could be an effective treatment. They helped design drugs which blocked aromatase, an enzyme involved in the production of oestrogens.

The first two generations of these aromatase inhibitors included drugs called aminoglutethimide and formestane, and were followed by two third-generation drugs, anastrozole and letrozole.

The ICR, and our partner hospital, The Royal Marsden, played a key role in assessing anastrozole and letrozole in patients. Professor Mitch Dowsett led the team that ran phase I trials of the drugs, leading to much larger studies and their route to patients.

International trials followed

Professor Dowsett also formed, with colleagues in the UK, a large international group of researchers who ran a clinical trial across 21 countries around the world, testing anastrazole against an older and widely used alternative drug, tamoxifen.

They looked at the drugs on their own and in combination and excitingly found that aromatase inhibitors were better than tamoxifen at preventing the recurrence of oestrogen receptor-positive breast cancers. Following the study, international guidance was quickly changed to recommend this type of treatment.

Alongside the trial, Professor Dowsett was also thinking about ways to identify any women who might particularly benefit.

By analysing 2,000 samples taken from women on the international trial, his team found biomarkers which could be used to identify those who would benefit the most.

Practice-changing research

The team went on to turn this discovery into a test which is now used by doctors to work out who should be given aromatase inhibitors alone rather than with chemotherapy, which can have severe side-effects and isn’t needed by all women.

More recently, the ICR Clinical Trials and Statistics Unit, led by Professor Judith Bliss, played an instrumental role in a phase III study of another aromatase inhibitor, exemestane. The results of the trial were published in 2014 and led to new recommendations for how it should be used in the clinic.

Overall this work has changed the way doctors treat oestrogen receptor-positive breast cancers across the world, saving the lives of thousands of women every year, and sparing many from unnecessary chemotherapy.