title: Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification.
abstract: OBJECTIVE
  Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer.
  
  
  METHODS
  Breast biopsies from 93 HER-2-positive patients treated with trastuzumab-based neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+.
  
  
  RESULTS
  HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low- and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low- plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen, T or N stage, tumor grade, or hormonal receptors.
  
  
  CONCLUSIONS
  This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.
authors.affiliation: CLCC G-F Leclerc and 1FR100, Dijon, France. larnould@dijon.fnclcc.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnould
authors.forename: Patrick
authors.initials: P
authors.lastname: Arveux
authors.forename: Jerome
authors.initials: J
authors.lastname: Couturier
authors.forename: Marion
authors.initials: M
authors.lastname: Gelly-Marty
authors.forename: Catherine
authors.initials: C
authors.lastname: Loustalot
authors.forename: Francette
authors.initials: F
authors.lastname: Ettore
authors.forename: Christine
authors.initials: C
authors.lastname: Sagan
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.forename: Frederique
authors.initials: F
authors.lastname: Penault-Llorca
authors.forename: Berangere
authors.initials: B
authors.lastname: Vasseur
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Coudert
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human