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
DOI/URL:
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Clifford Hudis
    813 Hudis
  2. Larry Norton
    532 Norton
  3. Mark E Robson
    355 Robson
  4. David Solit
    417 Solit
  5. Chau Dang
    153 Dang
  6. Maura N Dickler
    234 Dickler
  7. Ronglai Shen
    125 Shen
  8. Marc Ladanyi
    840 Ladanyi
  9. Tiffany A Traina
    145 Traina
  10. Shanu Modi
    128 Modi
  11. David Hyman
    175 Hyman
  12. Komal Lachhman Jhaveri
    39 Jhaveri
  13. Agnes Viale
    202 Viale
  14. Ahmet Zehir
    143 Zehir
  15. Edi Brogi
    301 Brogi
  16. Michael Forman Berger
    372 Berger
  17. Dara Stacy Ross
    42 Ross
  18. Barry Stephen Taylor
    135 Taylor
  19. Nikolaus D Schultz
    192 Schultz
  20. Britta Weigelt
    256 Weigelt
  21. Jorge Sergio Reis
    280 Reis
  22. Jose T Baselga
    383 Baselga
  23. Pedram Razavi
    23 Razavi
  24. Matthew   Chang
    21 Chang
  25. Cyriac Kandoth
    16 Kandoth
  26. Bob Tingkan Li
    56 Li
  27. Lillian   Smyth
    20 Smyth
  28. Sumit   Middha
    51 Middha
  29. Karl Philip Jonsson
    18 Jonsson
  30. Alexander Vincent Penson
    14 Penson
  31. Ritika   Kundra
    14 Kundra
  32. Neil Vasan
    3 Vasan
  33. Michael Lain Cheng
    4 Cheng
  34. Guotai Xu
    1 Xu
  35. Yanyan Cai
    2 Cai
  36. Ruchi Patel
    2 Patel
  37. Wen Zhang
    1 Zhang