title: Response-guided neoadjuvant chemotherapy for breast cancer.
abstract: OBJECTIVE
  We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer.
  
  
  METHODS
  We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery.
  
  
  RESULTS
  DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor-positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor-negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74).
  
  
  CONCLUSIONS
  This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor-positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.
authors.affiliation: Gunter von Minckwitz, Keyur Mehta, and Sibylle Loibl, Headquarters, German Breast Group, Neu-Isenburg; Jens Uwe Blohmer, St Gertrauden Krankenhaus, Berlin); Serban Dan Costa, Universitäts-Frauenklinik, Magdeburg; Carsten Denkert, Institute for Pathology, Charite, Berlin; Holger Eidtmann, Universitäts-Frauenklink, Kiel; Wolfgang Eiermann and Claus Hanusch, Klinikum zum Roten Kreuz, Munich; Bernd Gerber, Universitäts-Frauenklinik, Rostock; Jörn Hilfrich, Henrietten-Stiftung, Hanover; Jens Huober, Universitäts-Frauenklinik Tübingen, Frauenklinik; Christian Jakisch and Sibylle Loibl, Städtische Kliniken, Offenbach; Gunter von Minckwitz, Universitäts-Frauenklinik, Frankfurt; Sherko Kümmel, Klinikum Essen Mitte, Essen; Stefan Paepke, Universitäts-Frauenklinik rechts der Isar, Munich; Andreas Schneeweiss, National Center for Tumor Diseases, University of Heidelberg; Michael Untch, Helios-Klinikum, Berlin-Buch; Dirk Michael Zahm, Brustzentrum Stiftung Rehabilitation Heidelberg (SRH) Waldkliniken, Gera, Germany; Jens Huober, Kantonsspital, St Gallen, Switzerland.
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Jens Uwe
authors.initials: JU
authors.lastname: Blohmer
authors.forename: Serban Dan
authors.initials: SD
authors.lastname: Costa
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Claus
authors.initials: C
authors.lastname: Hanusch
authors.forename: Jörn
authors.initials: J
authors.lastname: Hilfrich
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Sherko
authors.initials: S
authors.lastname: Kümmel
authors.forename: Stefan
authors.initials: S
authors.lastname: Paepke
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Dirk Michael
authors.initials: DM
authors.lastname: Zahm
authors.forename: Keyur
authors.initials: K
authors.lastname: Mehta
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human