Title |
The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers
|
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Published in |
Cancer Cell, September 2018
|
DOI | 10.1016/j.ccell.2018.08.008 |
Pubmed ID | |
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, José Baselga |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 37 | 42% |
United Kingdom | 6 | 7% |
Italy | 5 | 6% |
Canada | 3 | 3% |
Spain | 2 | 2% |
Australia | 2 | 2% |
Belgium | 1 | 1% |
Finland | 1 | 1% |
Israel | 1 | 1% |
Other | 5 | 6% |
Unknown | 25 | 28% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 46 | 52% |
Scientists | 34 | 39% |
Practitioners (doctors, other healthcare professionals) | 6 | 7% |
Science communicators (journalists, bloggers, editors) | 2 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 582 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 104 | 18% |
Researcher | 96 | 16% |
Student > Bachelor | 42 | 7% |
Student > Master | 37 | 6% |
Other | 28 | 5% |
Other | 84 | 14% |
Unknown | 191 | 33% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 162 | 28% |
Medicine and Dentistry | 102 | 18% |
Agricultural and Biological Sciences | 45 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 16 | 3% |
Unspecified | 7 | 1% |
Other | 40 | 7% |
Unknown | 210 | 36% |