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:
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
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MSK Authors
  1. Clifford Hudis
    904 Hudis
  2. Larry Norton
    734 Norton
  3. Mark E Robson
    644 Robson
  4. David Solit
    729 Solit
  5. Chau Dang
    257 Dang
  6. Maura N Dickler
    262 Dickler
  7. Ronglai Shen
    192 Shen
  8. Marc Ladanyi
    1277 Ladanyi
  9. Tiffany A Traina
    233 Traina
  10. Shanu Modi
    239 Modi
  11. David Hyman
    352 Hyman
  12. Komal Lachhman Jhaveri
    162 Jhaveri
  13. Agnes Viale
    241 Viale
  14. Ahmet Zehir
    336 Zehir
  15. Edi Brogi
    480 Brogi
  16. Michael Forman Berger
    701 Berger
  17. Dara Stacy Ross
    116 Ross
  18. Barry Stephen Taylor
    236 Taylor
  19. Nikolaus D Schultz
    429 Schultz
  20. Britta Weigelt
    544 Weigelt
  21. Jose T Baselga
    483 Baselga
  22. Maurizio Scaltriti
    169 Scaltriti
  23. Pedram Razavi
    142 Razavi
  24. Matthew   Chang
    28 Chang
  25. Cyriac Kandoth
    31 Kandoth
  26. Bob Tingkan Li
    231 Li
  27. Lillian   Smyth
    42 Smyth
  28. Sumit   Middha
    82 Middha
  29. Karl Philip Jonsson
    50 Jonsson
  30. Alexander Vincent Penson
    53 Penson
  31. Ritika   Kundra
    76 Kundra
  32. Craig Bielski
    23 Bielski
  33. Neil Vasan
    19 Vasan
  34. Michael Lain Cheng
    15 Cheng
  35. Guotai Xu
    14 Xu
  36. Yanyan Cai
    15 Cai
  37. Ruchi Patel
    2 Patel
  38. Wen Zhang
    1 Zhang