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
    891 Hudis
  2. Larry Norton
    660 Norton
  3. Mark E Robson
    453 Robson
  4. David Solit
    541 Solit
  5. Chau Dang
    195 Dang
  6. Maura N Dickler
    252 Dickler
  7. Ronglai Shen
    143 Shen
  8. Marc Ladanyi
    1041 Ladanyi
  9. Tiffany A Traina
    178 Traina
  10. Shanu Modi
    161 Modi
  11. David Hyman
    301 Hyman
  12. Komal Lachhman Jhaveri
    66 Jhaveri
  13. Agnes Viale
    215 Viale
  14. Ahmet Zehir
    212 Zehir
  15. Edi Brogi
    385 Brogi
  16. Michael Forman Berger
    497 Berger
  17. Dara Stacy Ross
    71 Ross
  18. Barry Stephen Taylor
    189 Taylor
  19. Nikolaus D Schultz
    258 Schultz
  20. Britta Weigelt
    346 Weigelt
  21. Jorge Sergio Reis
    382 Reis
  22. Jose T Baselga
    461 Baselga
  23. Maurizio Scaltriti
    125 Scaltriti
  24. Pedram Razavi
    60 Razavi
  25. Matthew   Chang
    24 Chang
  26. Cyriac Kandoth
    27 Kandoth
  27. Bob Tingkan Li
    99 Li
  28. Lillian   Smyth
    31 Smyth
  29. Sumit   Middha
    77 Middha
  30. Karl Philip Jonsson
    41 Jonsson
  31. Alexander Vincent Penson
    31 Penson
  32. Ritika   Kundra
    31 Kundra
  33. Craig Bielski
    12 Bielski
  34. Neil Vasan
    8 Vasan
  35. Michael Lain Cheng
    11 Cheng
  36. Guotai Xu
    7 Xu
  37. Yanyan Cai
    7 Cai
  38. Ruchi Patel
    2 Patel
  39. Wen Zhang
    1 Zhang