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:
Notes: Export Date: 2 October 2015 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Larry Norton
    760 Norton
  2. Lu Wang
    147 Wang
  3. Rita Sakr
    61 Sakr
  4. Britta Weigelt
    643 Weigelt
  5. Francois-Clement Bidard
    17 Bidard
  6. Kiu Yan Charlotte Ng
    155 Ng
  7. Raymond Sear Lim
    57 Lim