Synapse - The genomic landscape of endocrine-resistant advanced breast cancers

The genomic landscape of endocrine-resistant advanced breast cancers Journal Article

Authors:	Razavi, P.; Chang, M. T.; Xu, G.; Bandlamudi, C.; Ross, D. S.; Vasan, N.; Cai, Y.; Bielski, C. M.; Donoghue, M. T. A.; Jonsson, P.; Penson, A.; Shen, R.; Pareja, F.; Kundra, R.; Middha, S.; Cheng, M. L.; Zehir, A.; Kandoth, C.; Patel, R.; Huberman, K.; Smyth, L. M.; Jhaveri, K.; Modi, S.; Traina, T. A.; Dang, C.; Zhang, W.; Weigelt, B.; Li, B. T.; Ladanyi, M.; Hyman, D. M.; Schultz, N.; Robson, M. E.; Hudis, C.; Brogi, E.; Viale, A.; Norton, L.; Dickler, M. N.; Berger, M. F.; Iacobuzio-Donahue, C. A.; Chandarlapaty, S.; Scaltriti, M.; Reis-Filho, J. S.; Solit, D. B.; Taylor, B. S.; Baselga, J.
Article Title:	The genomic landscape of endocrine-resistant advanced breast cancers
Abstract:	We integrated the genomic sequencing of 1,918 breast cancers, including 1,501 hormone receptor-positive tumors, with detailed clinical information and treatment outcomes. In 692 tumors previously exposed to hormonal therapy, we identified an increased number of alterations in genes involved in the mitogen-activated protein kinase (MAPK) pathway and in the estrogen receptor transcriptional machinery. Activating ERBB2 mutations and NF1 loss-of-function mutations were more than twice as common in endocrine resistant tumors. Alterations in other MAPK pathway genes (EGFR, KRAS, among others) and estrogen receptor transcriptional regulators (MYC, CTCF, FOXA1, and TBX3) were also enriched. Altogether, these alterations were present in 22% of tumors, mutually exclusive with ESR1 mutations, and associated with a shorter duration of response to subsequent hormonal therapies. Razavi et al. identify mutations in the MAPK pathway and the estrogen receptor transcriptional program in 22% of hormone receptor-positive breast cancers after hormone therapy. These mutations are mutually exclusive with ESR1 mutations and correlate with a shorter response duration to subsequent hormone therapies. © 2018 Elsevier Inc.
Keywords:	metastasis; breast cancer; cancer genomics; endocrine resistance; integrative genomics analysis
Journal Title:	Cancer Cell
Volume:	34
Issue:	3
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2018-09-10
Start Page:	427
End Page:	438.e6
Language:	English
DOI:	10.1016/j.ccell.2018.08.008
PROVIDER:	scopus
PUBMED:	30205045
PMCID:	PMC6327853
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052735603&doi=10.1016%2fj.ccell.2018.08.008&partnerID=40&md5=c1c0e86bf472e72609ae7c457962c6f9
Notes:	Article -- Export Date: 1 October 2018 -- Source: Scopus