@article{e7747e320dff4e9b982f99260a679f8f,
title = "Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers",
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.",
author = "Miller, {Christopher A.} and Yevgeniy Gindin and Charles Lu and Griffith, {Obi L.} and Malachi Griffith and Dong Shen and Jeremy Hoog and Tiandao Li and Larson, {David E.} and Mark Watson and Davies, {Sherri R.} and Kelly Hunt and Suman, {Vera J.} and Jacqueline Snider and Thomas Walsh and Colditz, {Graham A.} and Katherine Deschryver and Wilson, {Richard K.} and Mardis, {Elaine R.} and Ellis, {Matthew J.}",
note = "Funding Information: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also supported in part by funding provided by grants U54HG003079 from the National Human Genome Research Institute to R.K.W., R01-CA095614 to M.J.E., U24-CA114736, U10-CA076001, and U01-CA114722 from the National Cancer Institute; by the Breast Cancer Research Foundation; Komen Promise Grant PG12220321 to M.J.E., a Komen St Louis Affiliate Clinical Trials Grant; and support for Z1031 from Pfizer and Novartis. M.J.E. is a McNair Medical Foundation Scholar",
year = "2016",
month = aug,
day = "9",
doi = "10.1038/ncomms12498",
language = "English",
volume = "7",
journal = "Nature communications",
issn = "2041-1723",
}