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Ref Type Journal Article
PMID (25953157)
Authors Bidard FC, Ng CK, Cottu P, Piscuoglio S, Escalup L, Sakr RA, Reyal F, Mariani P, Lim R, Wang L, Norton L, Servois V, Sigal B, Vincent-Salomon A, Weigelt B, Pierga JY, Reis-Filho JS
Title Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer.
Journal Vol Issue Date Pages Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology 26 8 2015 Aug 1704-9 Ann Oncol
URL
Abstract Text HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2.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.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.This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.

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Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB3 G284R breast cancer predicted - sensitive Lapatinib + Trastuzumab Case Reports/Case Series Actionable In a clinical case study, the combination treatment of Herceptin (trastuzumab) and Tykerb (lapatinib) in a patient with breast cancer harboring ERBB3 (HER3) G284R resulted in antitumor efficacy, demonstrating a complete metabolic response after day 14 of treatment, a partial response after 8 weeks of treatment, and no clinical evidence of disease after 40 weeks of treatment (PMID: 25953157). 25953157