Breast cancer genome sequencing has identified HER2-activating mutations in cancers that are HER2-negative by immunohistochemistry or fluorescence in situ hybridization.1,2 These HER2-activating mutations cause an oncogenic transformation of breast epithelial cells in tissue culture and increase tumor growth in xenograft models.2,3 The sensitivity of these HER2-activating mutations to HER2-targeted drugs has been measured,2,4 and 2 clinical trials are screening patients with metastatic breast cancer for HER2 mutations, and treating patients with HER2-positive breast cancer with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib (HKI-272) (ClinicalTrials.gov identifiers: NCT01670877 and NCT01953926). This report describes the first case of a HER2-mutated breast cancer that clinically benefited from neratinib monotherapy. When this patient's cancer progressed, she was placed on neratinib plus capecitabine combination therapy and she again experienced response.
Dr. Bose has disclosed that he is a consultant for Genentech, Inc., and has received honoraria from the speaker's bureaus of Novartis Pharmaceuticals Corporation and RGA International. Dr. Kavuri has disclosed that he has no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Dr. Ma is the principal investigator of a phase II clinical trial funded in part by Puma Biotechnology, Inc.; Drs. Bose and Ellis are subinvestigators on this trial. Dr. Ellis has ownership interest (including patents) in Bioclassifier LLC and has performed ad hoc consulting for Puma Biotechnology, Inc., Genentech, Inc., Novartis Pharmaceuticals Corporation, AstraZeneca Pharmaceuticals LP, and Pfizer Inc.
This work was supported by the NIH (grant R01CA161001 to R. Bose and R01CA095614 to M.J. Ellis) and the Siteman Cancer Center-Foundation for Barnes-Jewish Hospital Cancer Frontier Fund.
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