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Plasma ESR1 Mutations

Dr Fribbens has been looking at the presence of oestrogen receptor (ESR1) mutations in ctDNA in patients with metastatic breast cancer who are taking hormone therapy. This treatment is very successful in many women with ER positive breast cancer but over time women can develop resistance to the treatment. We know that when some patients become resistant they may have ESR1 mutations detected in DNA in their blood sample. Dr Fribbens initial research provided the first evidence that we can use results from liquid biopsies to choose hormone therapy for these patients. Detection of the ESR1 mutation in blood suggests relative resistance to a drug exemestane and relative sensitivity to the drug fulvestrant.

This was presented at the American Association for Cancer Research conference and published as a lead editorial in the Journal of Clinical Oncology.

Dr Fribbens then developed this research further with the aim to identify the length of time between the first point when ESR1 mutations can be detected in blood and when the cancer progresses. Results show that ESR1 mutations are found in over half of patients progressing on hormone therapy and the emergence of these can be detected over six months before the cancer progresses. This could potentially be used in future so alternative treatments could be considered before the cancer becomes worse.

This work was presented at the American Society of Clinical Oncology conference in June and published in October 2017 in Annals of Oncology, the journal of the European Society for Medical Oncology.

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