Details

Autor(en) / Beteiligte

• Razavi, Pedram
• Chang, Matthew T.
• Xu, Guotai
• Bandlamudi, Chaitanya
• Ross, Dara S.
• Vasan, Neil
• Cai, Yanyan
• Bielski, Craig M.
• Donoghue, Mark T.A.
• Jonsson, Philip
• Penson, Alexander
• Shen, Ronglai
• Pareja, Fresia
• Kundra, Ritika
• Middha, Sumit
• Cheng, Michael L.
• Zehir, Ahmet
• Kandoth, Cyriac
• Patel, Ruchi
• Huberman, Kety
• Smyth, Lillian M.
• Jhaveri, Komal
• Modi, Shanu
• Traina, Tiffany A.
• Dang, Chau
• Zhang, Wen
• Weigelt, Britta
• Li, Bob T.
• Ladanyi, Marc
• Hyman, David M.
• Schultz, Nikolaus
• Robson, Mark E.
• Hudis, Clifford
• Brogi, Edi
• Viale, Agnes
• Norton, Larry
• Dickler, Maura N.
• Berger, Michael F.
• Iacobuzio-Donahue, Christine A.
• Chandarlapaty, Sarat
• Scaltriti, Maurizio
• Reis-Filho, Jorge S.
• Solit, David B.
• Taylor, Barry S.
• Baselga, José

Titel

The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers

Ist Teil von

• Cancer cell, 2018-09, Vol.34 (3), p.427-438.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •We performed prospective sequencing of 1,501 HR+ breast cancers in the clinical setting•MAPK and TF alterations were present in 22% of 692 HR+ post-endocrine therapy tumors•MAPK and TF alterations were mutually exclusive with ESR1 mutations•MAPK and TF alterations were associated with shorter response to endocrine 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.