title: Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study.
abstract: BACKGROUND
  Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab.
  
  
  METHODS
  Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes.
  
  
  RESULTS
  BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%-81%] and 47% (95% CI 36%-58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952-7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303-0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368-0.870) by multivariate analysis.
  
  
  CONCLUSIONS
  The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.
authors.affiliation: Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Torino, Italy. anna.sapino@unito.it
authors.forename: A
authors.initials: A
authors.lastname: Sapino
authors.forename: F
authors.initials: F
authors.lastname: Montemurro
authors.forename: C
authors.initials: C
authors.lastname: Marchiò
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.forename: J
authors.initials: J
authors.lastname: Kulka
authors.forename: M
authors.initials: M
authors.lastname: Donadio
authors.forename: A
authors.initials: A
authors.lastname: Bottini
authors.forename: G
authors.initials: G
authors.lastname: Botti
authors.forename: A P
authors.initials: AP
authors.lastname: dei Tos
authors.forename: A
authors.initials: A
authors.lastname: Bersiga
authors.forename: S
authors.initials: S
authors.lastname: Di Palma
authors.forename: M
authors.initials: M
authors.lastname: Truini
authors.forename: G
authors.initials: G
authors.lastname: Sanna
authors.forename: M
authors.initials: M
authors.lastname: Aglietta
authors.forename: G
authors.initials: G
authors.lastname: Bussolati
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001710:Biotin / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D000068878:Trastuzumab