title: HER2-Mutated Breast Cancer Responds to Treatment With Single-Agent Neratinib, a Second-Generation HER2/EGFR Tyrosine Kinase Inhibitor.
abstract: Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second-generation HER2/EGFR tyrosine kinase inhibitor neratinib resulted in partial response and dramatic improvement in the patient's functional status. This partial response lasted 11 months, and when the patient's cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2-amplified breast cancer after disease progression. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-mutated breast cancer. Two clinical trials of neratinib for HER2-mutated metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancers, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2-mutated solid tumors is warranted.
authors.affiliation: From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Noa Efrat
authors.initials: NE
authors.lastname: Ben-Baruch
authors.affiliation: From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Ron
authors.initials: R
authors.lastname: Bose
authors.affiliation: From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Shyam M
authors.initials: SM
authors.lastname: Kavuri
authors.affiliation: From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Cynthia X
authors.initials: CX
authors.lastname: Ma
authors.affiliation: From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas. From the Department of Oncology, Kaplan Medical Center, Rehovot, Israel; Section of Breast Oncology, Division of Oncology, Department of Medicine, Siteman Cancer Center, and Washington University School of Medicine, St. Louis, Missouri; and Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000069287:Capecitabine / Q000008:administration & dosage; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D019233:Retreatment
chemical_list: D000069287:Capecitabine; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C487932:neratinib