Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer Journal Article

  


Authors: Bidard, F. C.; Ng, C. K. Y.; Cottu, P.; Piscuoglio, S.; Escalup, L.; Sakr, R. A.; Reyal, F.; Mariani, P.; Lim, R.; Wang, L.; Norton, L.; Servois, V.; Sigal, B.; Vincent-Salomon, A.; Weigelt, B.; Pierga, J. Y.; Reis-Filho, J. S.
Article Title: Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer
Abstract: Background: HER3 activating mutations have been shown in preclinical models to be oncogenic and ligandindependent, but to depend on kinase-active HER2. Patients and methods: Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation. Results: HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis. Discussion: This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Keywords: breast cancer; massively parallel sequencing; precision medicine; dual her2 blockade; her3 mutations
Journal Title: Annals of Oncology
Volume: 26
Issue: 8
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2015-08-01
Start Page: 1704
End Page: 1709
Language: English
DOI: 10.1093/annonc/mdv217
PROVIDER: scopus
PUBMED: 25953157
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84941658031&partnerID=40&md5=b7589c7e5c710a8162beb75184fd0010
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Larry Norton
    762 Norton
  2. Lu Wang
    147 Wang
  3. Rita Sakr
    61 Sakr
  4. Britta Weigelt
    646 Weigelt
  5. Jorge Sergio Reis-Filho
    642 Reis-Filho
  6. Francois-Clement Bidard
    17 Bidard
  7. Kiu Yan Charlotte Ng
    155 Ng
  8. Salvatore Piscuoglio
    130 Piscuoglio
  9. Raymond Sear Lim
    59 Lim
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