title: HER2/neu-directed therapy for biliary tract cancer.
abstract: BACKGROUND
  Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular characterization have identified a subset of biliary patients that have HER2/neu amplification or mutation. HER2/neu amplification is associated with response to HER2/neu-directed therapy in breast and gastric cancers. However, the efficacy of HER2/neu-targeted therapy in biliary cancers is unknown.
  
  
  METHODS
  We retrospectively reviewed cases of advanced gallbladder cancer and cholangiocarcinoma with HER2/neu genetic aberrations or protein overexpression who received HER2/neu-directed therapy between 2007 and 2014. Clinical data were retrieved from medical records, and imaging studies were independently reviewed.
  
  
  RESULTS
  Nine patients with gallbladder cancer and five patients with cholangiocarcinoma had received HER2/neu-directed therapy (trastuzumab, lapatinib, or pertuzumab) during the study period. In the gallbladder cancer group, HER2/neu gene amplification or overexpression was detected in eight cases. These patients experienced disease stability (n = 3), partial response (n = 4), or complete response (n = 1) with HER2/neu-directed therapy. One patient had HER2/neu mutation and experienced a mixed response after lapatinib therapy. The duration of response varied from 8+ to 168 weeks (median 40 weeks), and three patients are still on therapy. One patient developed HER2/neu amplification as a secondary event after FGFR-directed therapy for FGF3-TACC3 gene fusion. The cholangiocarcinoma cases treated in this series had a higher proportion of HER2/neu mutations, and no radiological responses were seen in these patients despite HER2/neu-directed therapy.
  
  
  CONCLUSIONS
  HER2/neu blockade is a promising treatment strategy for gallbladder cancer patients with gene amplification and deserves further exploration in a multi-center study.
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA. mjavle@mdanderson.org.
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Churi
authors.affiliation: Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: HyunSeon C
authors.initials: HC
authors.lastname: Kang
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Rachna
authors.initials: R
authors.lastname: Shroff
authors.affiliation: Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.affiliation: Scott & White Clinic, Temple, TX, USA.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Surapaneni
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Zuo
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Barrera
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Humaid
authors.initials: H
authors.lastname: Alshamsi
authors.affiliation: Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Department of Gastroenterology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lopa
authors.initials: L
authors.lastname: Mishra
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit Number 426, Room Number FC10.3062, Houston, TX, 77030, USA.
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Kaseb
authors.affiliation: Gibbs Cancer Center & Research Institute, Spartanburg, SC, USA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: Thomas
authors.affiliation: Departments of Medicine and Surgery, Columbia University, 622 West 168th Street, PH-14, room 105 C, New York, NY, 10032, USA. aas54@cumc.columbia.edu.
authors.forename: Abby B
authors.initials: AB
authors.lastname: Siegel
mesh_terms: D000328:Adult; D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000628:therapy*; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human