title: Magnitude of trastuzumab benefit in patients with HER2-positive, invasive lobular breast carcinoma: results from the HERA trial.
abstract: OBJECTIVE
  To evaluate the benefit of adjuvant trastuzumab in patients diagnosed with human epidermal growth factor receptor 2 (HER2) -positive invasive lobular carcinoma (ILC) enrolled onto the Herceptin Adjuvant (HERA) trial.
  
  
  METHODS
  Patients randomly assigned to receive one year of trastuzumab and one year of observation in the HERA trial were included (n = 3,401). Centrally reviewed estrogen receptor (ER), progesterone receptor (PgR), and HER2 copy numbers were used. First site-specific relapse pattern was evaluated for ILC and invasive ductal carcinoma (IDC). The magnitude of trastuzumab benefit was assessed using the Cox proportional hazards model for disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  Median follow-up time was 4 years. A total of 187 ILC and 3,213 IDC patients were included. High Allred scores (6 to 8) were more common in patients with ILC than IDC for both ER (36.9% v 22.7%) and PgR (44.1% v 28.5%). A trend toward decreased HER2 copy number was observed in the ILC group. The ILC and IDC subgroups had similar patterns of first site of disease relapse. DFS hazard ratios (HRs) comparing 1 year of trastuzumab versus observation were 0.63 for ILC (95% CI, 0.34 to 1.15) and 0.77 for IDC (95% CI, 0.67 to 0.89; P for interaction = .49). The OS HRs comparing 1 year of trastuzumab versus observation were 0.60 for ILC (95% CI, 0.27 to 1.31) and 0.86 for IDC (95% CI, 0.71 to 1.06; P for interaction = .29).
  
  
  CONCLUSIONS
  In this retrospective analysis, there was no suggestion that patients in the ILC cohort experienced a different magnitude of benefit from adjuvant trastuzumab than those in the IDC cohort.
authors.affiliation: Dana-Farber Cancer Institute, Harvard School of Public Health, Harvard Medical School, Boston, MA, USA.
authors.forename: Otto
authors.initials: O
authors.lastname: Metzger-Filho
authors.forename: Marion
authors.initials: M
authors.lastname: Procter
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.forename: Brian
authors.initials: B
authors.lastname: Leyland-Jones
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.forename: Kamal S
authors.initials: KS
authors.lastname: Saini
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Richard
authors.initials: R
authors.lastname: Bell
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart-Gebhart
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human