title: Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups.
abstract: OBJECTIVE
  To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.
  
  
  METHODS
  Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m(2)) followed by four 3-week cycles paclitaxel (175 mg/m(2)) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue.
  
  
  RESULTS
  Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure.
  
  
  CONCLUSIONS
  Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.
authors.affiliation: Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany. michael.untch@helios-kliniken.de
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Gottfried E
authors.initials: GE
authors.lastname: Konecny
authors.forename: Stephan
authors.initials: S
authors.lastname: Hasmüller
authors.forename: Annette
authors.initials: A
authors.lastname: Lebeau
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Oumar
authors.initials: O
authors.lastname: Camara
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kühn
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.forename: Nadia
authors.initials: N
authors.lastname: Harbeck
authors.forename: Cornelia
authors.initials: C
authors.lastname: Höss
authors.forename: Steffen
authors.initials: S
authors.lastname: Kahlert
authors.forename: Thomas
authors.initials: T
authors.lastname: Beck
authors.forename: Werner
authors.initials: W
authors.lastname: Fett
authors.forename: Keyur M
authors.initials: KM
authors.lastname: Mehta
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012074:Remission Induction; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D015251:Epirubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab