Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant

• DOI: 10.1038/ncomms11579
• Publication Date: 2016-05-13T11:07:59Z
• Authors: Jill M. Spoerke; Steven Gendreau; Kimberly Walter; Jiaheng Qiu; Timothy R. Wilson; Heidi Savage; Junko Aimi; Mika K. Derynck; Meng Chen; Iris T. Chan; Lukas C. Amler; Garret M. Hampton; Stephen Johnston; Ian Krop; Peter Schmid; Mark R. Lackner
• Keywords: Fulvestrant; Aromatase inhibitor; Estrogen receptor alpha

Abstract Mutations in ESR1 have been associated with resistance to aromatase inhibitor (AI) therapy patients ER+ metastatic breast cancer. Little is known of the impact these mutations receiving selective oestrogen receptor degrader (SERD) therapy. In this study, hotspot and PIK3CA from ctDNA were assayed clinical trial samples cancer randomized either SERD fulvestrant or plus a pan-PI3K inhibitor. are present 37% baseline enriched luminal A -mutated tumours. often polyclonal longitudinal analysis shows distinct clones exhibiting divergent behaviour over time. mutation allele frequency does not show consistent pattern increases during treatment, progression-free survival different compared wild-type patients. study.