title: Management and outcome of HER2-positive early breast cancer treated with or without trastuzumab in the adjuvant trastuzumab era.
abstract: BACKGROUND
  Adjuvant trastuzumab (AT) is known to significantly improve survival of women with HER2(+) early breast cancer. This study explores the use and nonuse of AT in early breast cancer, as well as the efficacy in a neoadjuvant and adjuvant population, within a routine clinical setting.
  
  
  METHODS
  Histopathology reports of invasive breast cancer resected at Imperial College Healthcare NHS Trust (ICHT) between January 2006 and December 2008 were reviewed. HER2(+) patients were identified and their case notes reviewed. In addition, patients who received AT at our center but underwent surgery elsewhere were included in the efficacy and safety analyses.
  
  
  RESULTS
  The local HER2(+) rate was 13.1%, with 54.5% of these patients receiving AT. A total of 128 patients received AT (85 local and 43 referrals from elsewhere). Neoadjuvant chemotherapy (CT) followed by postoperative AT was associated with a significantly increased risk of recurrence compared with adjuvant CT and then AT (hazard ratio [HR] 18.6 [95% CI, 1.8-152.2]; P = .013). The proportion of patients who were disease free at 3 years from primary therapy was 96.4% (95% CI, 89.8%-100%) for adjuvant therapy, compared with 72.0% (95% CI, 56.5%-91.6%) for neoadjuvant therapy. AT was omitted in 49 HER2(+) patients; the main reason for AT omission was clinical judgment that the breast cancer was low risk. Patients treated with AT had a significantly decreased risk of recurrence (HR 0.27 [95% CI, 0.08-0.97]; P = .04) compared with the untreated patients. The majority of untreated relapses were in patients in whom there was an original intent to use AT. The proportion alive at 3 years for adjuvant CT, neoadjuvant CT, and untreated AT was 100%, 74.5%, and 92.7% respectively.
  
  
  CONCLUSIONS
  The overall efficacy and safety of AT in our routine clinical setting is comparable to the large randomized trials. HER2(+) patients who underwent neoadjuvant CT had a significantly increased risk of disease recurrence compared with patients treated with adjuvant CT followed by trastuzumab. Untreated patients had an increased risk of recurrence.
authors.affiliation: Cancer Research UK Laboratories, Division of Cancer, Imperial College London, UK. c.palmieri@imperial.ac.uk
authors.forename: Carlo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Deep
authors.initials: D
authors.lastname: Shah
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krell
authors.forename: Ondrej
authors.initials: O
authors.lastname: Gojis
authors.forename: Katy
authors.initials: K
authors.lastname: Hogben
authors.forename: Pippa
authors.initials: P
authors.lastname: Riddle
authors.forename: Riz
authors.initials: R
authors.lastname: Ahmad
authors.forename: Tri
authors.initials: T
authors.lastname: Tat
authors.forename: Kevin
authors.initials: K
authors.lastname: Fox
authors.forename: Andrew
authors.initials: A
authors.lastname: Porter
authors.forename: Sarah
authors.initials: S
authors.lastname: Mahmoud
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kirschke
authors.forename: Sami
authors.initials: S
authors.lastname: Shousha
authors.forename: Mihir
authors.initials: M
authors.lastname: Gudi
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Robert
authors.initials: R
authors.lastname: Leonard
authors.forename: Susan
authors.initials: S
authors.lastname: Cleator
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab