Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer.
Ann Oncol
; 26(8): 1704-9, 2015 Aug.
Article
en En
| MEDLINE
| ID: mdl-25953157
ABSTRACT
BACKGROUND:
HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2. PATIENTS ANDMETHODS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Receptor ErbB-2
/
Receptor ErbB-3
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos