title: Long-term follow-up after preoperative trastuzumab and chemotherapy for HER2-overexpressing breast cancer.
abstract: BACKGROUND
  Neoadjuvant chemotherapy and trastuzumab is an established treatment for locally advanced HER2-positive breast cancer, providing favorable rates of clinical response and pCR. Minimal data describe long-term outcomes after neoadjuvant HER2-directed therapy. This study aimed to explore long-term efficacy and toxicity after neoadjuvant trastuzumab and chemotherapy for HER2-positive breast cancer.
  
  
  METHODS
  Eligible patients participated in 1 of 2 single-arm phase II neoadjuvant trials, receiving either paclitaxel/trastuzumab (TH) or vinorelbine/trastuzumab (NH) for stage II-III HER2-positive disease. Postoperative chemotherapy, with or without trastuzumab, was offered. Charts were reviewed to identify recurrence, death, and treatment-related toxicities. Association of long-term outcomes with baseline characteristics and pathological response to primary therapy was explored.
  
  
  RESULTS
  Eighty patients were identified; 33 (41.3%) received TH and 47 (58.8%) received NH. Fourteen (17.5%) had pCR at surgery. Most (96.3%) received anthracycline-based adjuvant chemotherapy; 78.7% of NH patients also received adjuvant trastuzumab. At a median follow-up of 8.8 years, 23 (28.8%) patients have experienced recurrence, with 16 breast cancer-related deaths. Four-year RFS in patients with pCR was 92.9% (95% confidence interval [CI], 79.4%-100%) versus 72.4% without pCR (95% CI, 63.9%-82.1%). All initial symptomatic cardiotoxicity resolved during extended follow-up. New symptomatic cardiotoxicity in long-term follow-up was rare, primarily occurring in patients requiring retreatment with a cardiotoxic agent.
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer resulted in favorable long-term survival with minimal late toxicity. Trends in this data set suggest an association between pCR and improved long-term RFS. Retreatment with cardiotoxic agents might increase risk of late cardiotoxicity.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA. Electronic address: emayer@partners.org.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Mayer
authors.affiliation: Brigham and Women's Hospital, Boston, MA.
authors.forename: Adrienne B
authors.initials: AB
authors.lastname: Gropper
authors.affiliation: Case Comprehensive Cancer Center, Cleveland, OH.
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Harris
authors.affiliation: Mt Kisco Medical Group, Mt Kisco, NY.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gold
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Leroy
authors.initials: L
authors.lastname: Parker
authors.affiliation: Massachusetts General Hospital, Boston, MA.
authors.forename: Irene
authors.initials: I
authors.lastname: Kuter
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Steven
authors.initials: S
authors.lastname: Come
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Najita
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D057234:Preoperative Period; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Anthracycline; Cardiotoxicity; Neoadjuvant therapy; Pathologic complete response