Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers

Year: 2016

Type: article

Abstract: Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor-positive (ER+) breast cancer. To better understand the contributions of tumour heterogeneity and evolution to resistance, here we perform comprehensive genomic characterization of 22 primary tumours sampled before and after 4 months of neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome sequencing of tumour/normal pairs from the two time points, with coincident tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity, with marked remodelling of the clonal landscape in response to NAI. Two cases have genomic evidence of two independent tumours, most obviously an ER- 'collision tumour', which was only detected after NAI treatment of baseline ER+ disease. Many mutations are newly detected or enriched post treatment, including two ligand-binding domain mutations in ESR1. The observed clonal complexity of the ER+ breast cancer genome suggests that precision medicine approaches based on genomic analysis of a single specimen are likely insufficient to capture all clinically significant information.

Source: Nature Communications

DOI: 10.1038/ncomms12498

Institutions: Washington University in St. Louis, Takara (United States), AbbVie (United States), AstraZeneca (United States), The University of Texas MD Anderson Cancer Center, Mayo Clinic, Baylor College of Medicine

Language: English

Topic: Cancer Genomics and Diagnostics

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: Breast Cancer Research Foundation, Pfizer, Cancer Prevention and Research Institute of Texas, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute

OpenAlex ID: W2493364589