Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations

• DOI: 10.1038/s41416-018-0345-x
• Publication Date: 2018-12-12T18:07:13Z
• Authors: Elena Lopez-Knowles; Alex Pearson; Gene Schuster; Pascal Gellert; Ricardo Ribas; Belinda Yeo; Ros Cutts; Richard Buus; Isaac Garcia-Muri...; Ben Haynes; Lesley-Ann Martin; Ian Smith; Nick Turner; Mitch Dowsett
• Keywords: Estrogen receptor alpha; CDH1; Aromatase inhibitor

Several thousand breast cancer patients develop resistance to aromatase inhibitors (AIs) each year in the UK. Rational treatment requires an improved molecular characterisation of resistant disease. The mutational landscape 198 regions 16 key genes and RNA expression 209 covering pathways was evaluated paired biopsies before AI at progression on from 48 patients. Validity findings assessed another five ESR1-mutated tumours progressing AI. Eighty-nine mutations were identified 41 matched pairs (PIK3CA 27%; CDH1 20%). ESR1 (n = 5), ERBB2 1) MAP2K4 had secondary sample only. There very high heterogeneity gene between AI-resistant with few patterns apparent. However, tumours, four classical oestrogen-regulated (ERGs) sevenfold higher than wild-type a finding confirmed second set tumours. In ERG remained suppressed uncoupled recovery seen proliferation. Major genotypic phenotypic exists appear drive processes