Uncommon mutations in three genes in oestrogen receptor positive breast cancer have a negative impact on disease prognosis according to a study published in Nature Communications this week.

The outcome of oestrogen receptor positive breast cancer is highly variable, and the impact of uncommon mutations on disease prognosis is not well known. Mutations in DNA can cause alterations in cell biology and lead to cancer, but understanding how rarer mutations link to disease outcome is difficult. Unravelling the link between uncommon mutations and prognosis in oestrogen receptor positive breast cancer requires the use of long-term clinical follow-up data, as well as genetic data.

Matthew Ellis and colleagues studied archival breast cancer DNA from three cohorts of post-menopausal (625) and pre-menopausal (328) patients with hormone receptor-positive breast cancer. Using archival formalin-fixed paraffin embedded tissue and targeted sequencing of 83 genes, the authors found associations with poor clinical outcomes in oestrogen receptor positive breast cancer for mutations in the genes NF1, PIK3R1, and DDR1.

The research shows that uncommon recurrent mutations can impact prognosis, which could help to explain the highly variable outcomes observed in oestrogen receptor positive breast cancer.