title: Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort.
abstract: BACKGROUND
  The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.
  
  
  METHODS
  We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.
  
  
  RESULTS
  Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61-78; n=36 events] with trastuzumab, vs 56% [46-65; n=51 events] without; hazard ratio 0.59 [95% CI 0.38-0.90]; p=0.013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.
  
  
  CONCLUSIONS
  The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.
  
  
  BACKGROUND
  F Hoffmann-La Roche.
authors.affiliation: Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. luca.gianni@istitutotumori.mi.it
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Vladimir
authors.initials: V
authors.lastname: Semiglazov
authors.forename: Alexey
authors.initials: A
authors.lastname: Manikhas
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Sergey
authors.initials: S
authors.lastname: Tjulandin
authors.forename: Milvia
authors.initials: M
authors.lastname: Zambetti
authors.forename: Federico
authors.initials: F
authors.lastname: Vazquez
authors.forename: Mikhail
authors.initials: M
authors.lastname: Byakhow
authors.forename: Mikhail
authors.initials: M
authors.lastname: Lichinitser
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Climent
authors.forename: Eva
authors.initials: E
authors.lastname: Ciruelos
authors.forename: Belén
authors.initials: B
authors.lastname: Ojeda
authors.forename: Mauro
authors.initials: M
authors.lastname: Mansutti
authors.forename: Alla
authors.initials: A
authors.lastname: Bozhok
authors.forename: Roberta
authors.initials: R
authors.lastname: Baronio
authors.forename: Andrea
authors.initials: A
authors.lastname: Feyereislova
authors.forename: Claire
authors.initials: C
authors.lastname: Barton
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007262:Infusions, Intravenous; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects*; D013997:Time Factors; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D005472:Fluorouracil; D008727:Methotrexate; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab