Title |
Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers
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Published in |
Nature Communications, August 2016
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DOI | 10.1038/ncomms12498 |
Pubmed ID | |
Authors |
Christopher A. Miller, Yevgeniy Gindin, Charles Lu, Obi L Griffith, Malachi Griffith, Dong Shen, Jeremy Hoog, Tiandao Li, David E. Larson, Mark Watson, Sherri R Davies, Kelly Hunt, Vera J. Suman, Jacqueline Snider, Thomas Walsh, Graham A. Colditz, Katherine DeSchryver, Richard K. Wilson, Elaine R. Mardis, Matthew J. Ellis |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 18 | 49% |
Saudi Arabia | 3 | 8% |
Belgium | 1 | 3% |
Spain | 1 | 3% |
Canada | 1 | 3% |
Unknown | 13 | 35% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 18 | 49% |
Members of the public | 17 | 46% |
Science communicators (journalists, bloggers, editors) | 2 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | <1% |
Netherlands | 1 | <1% |
France | 1 | <1% |
Australia | 1 | <1% |
United Kingdom | 1 | <1% |
Spain | 1 | <1% |
Unknown | 106 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 28 | 25% |
Student > Ph. D. Student | 21 | 19% |
Professor > Associate Professor | 8 | 7% |
Student > Master | 7 | 6% |
Other | 6 | 5% |
Other | 21 | 19% |
Unknown | 21 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 27 | 24% |
Agricultural and Biological Sciences | 27 | 24% |
Medicine and Dentistry | 23 | 21% |
Mathematics | 2 | 2% |
Computer Science | 2 | 2% |
Other | 5 | 4% |
Unknown | 26 | 23% |