The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2018 Sep 12

PMID 30205045

Citations 493

Authors

Pedram Razavi

Matthew T Chang

Guotai Xu

Chaitanya Bandlamudi

Dara S Ross

Neil Vasan

Yanyan Cai

Craig M Bielski

Mark T A Donoghue

Philip Jonsson

Alexander Penson

Ronglai Shen

Fresia Pareja

Ritika Kundra

Sumit Middha

Michael L Cheng

Ahmet Zehir

Cyriac Kandoth

Ruchi Patel

Kety Huberman

Lillian M Smyth

Komal Jhaveri

Shanu Modi

Tiffany A Traina

Chau Dang

Wen Zhang

Britta Weigelt

Bob T Li

Marc Ladanyi

David M Hyman

Nikolaus Schultz

Mark E Robson

Clifford Hudis

Edi Brogi

Agnes Viale

Larry Norton

Maura N Dickler

Michael F Berger

Christine A Iacobuzio-Donahue

Sarat Chandarlapaty

Maurizio Scaltriti

Jorge S Reis-Filho

David B Solit

Barry S Taylor

Jose Baselga

Affiliations

Soon will be listed here.

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.

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