title: Long-term outcome of the REMAGUS 02 trial, a multicenter randomised phase II trial in locally advanced breast cancer patients treated with neoadjuvant chemotherapy with or without celecoxib or trastuzumab according to HER2 status.
abstract: The REMAGUS-02 multicenter randomised phase II trial showed that the addition to neoadjuvant chemotherapy (NAC) of trastuzumab in patients with localised HER2-positive breast cancer (BC) increased the pathological complete response (pCR) rate and that the addition of celecoxib in HER2-negative cases did not increase the pCR rate. We report here the long-term follow-up results for disease-free survival (DFS) and overall survival (OS).
  
  
  
  From 2004 to 2007, 340 stage II-III BC patients were randomly assigned to receive neoadjuvant EC-T (four cycles of epirubicin-cyclophosphamide followed by four cycles of docetaxel) +/- celecoxib in HER2-negative cases (n = 220) and ± trastuzumab in HER2-positive cases (n = 120). From September 2005, all patients with HER2-positive BC received adjuvant T (n = 106).
  
  
  
  Median follow-up was nearly 8 years (94.4 months, 20-127 m). In the HER2-negative subgroup, addition of celecoxib was not associated with a DFS benefit. Favourable factors were smaller tumour size, expression of progesterone receptor status (PgR) and pCR. In the HER2-positive population, neoadjuvant trastuzumab was not associated with a DFS benefit. Axillary pCR was the only prognostic factor associated with DFS in this group [HR = 0.44, 95% CI = 0.2-0.97], p = 0.035]. To note, DFS and OS were significantly higher in the HER2-positive than in HER2-negative BC patients (HR = 0.58 [0.36-0.92], p = 0.021).
  
  
  
  Celecoxib combined with NAC provided neither pCR nor survival benefit in patients with HER2-negative BC. Absence of PgR is a major prognostic factor. Neoadjuvant trastuzumab increased pCR rates without translation into a DFS or OS benefit compared with adjuvant trastuzumab only. Axillary pCR could be a more relevant surrogate of survival than in the breast in HER2-positive population. A retrospective comparison shows that patients with HER2-positive tumours have a better outcome than HER2-negative BC patients showing the impact of trastuzumab on the natural history of BC.
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, 75475 Paris, France. Electronic address: sylvie.giacchetti@aphp.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giacchetti
authors.affiliation: Institut Curie, PSL Research University, Translational Research Department, INSERM, U932 Immunity and Cancer, Residual Tumor & Response to Treatment Laboratory (RT2Lab), Paris, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Hamy
authors.affiliation: Medical Oncology Department, Gustave Roussy, Cancer Center Villejuif, France.
authors.forename: Suzette
authors.initials: S
authors.lastname: Delaloge
authors.affiliation: Medical Oncology Department, Institut Curie, Saint Cloud, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Brain
authors.affiliation: Biostatistics Department, Institut Curie, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Berger
authors.affiliation: Tumor Biology Department, Institut Curie, Saint Cloud, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sigal-Zafrani
authors.affiliation: Pathology Department, Gustave Roussy, Cancer Center Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mathieu
authors.affiliation: AP-HP, Hôpital Saint-Louis, Pathology Department, University Paris Diderot, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertheau
authors.affiliation: Tumor Biology Department, Institut Curie, Saint Cloud, Paris, France.
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Guinebretière
authors.affiliation: Medical Oncology Department, Gustave Roussy, Cancer Center Villejuif, France.
authors.forename: Mahasti
authors.initials: M
authors.lastname: Saghatchian
authors.affiliation: Medical Oncology Department, Institut Curie, Saint Cloud, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Lerebours
authors.affiliation: Department of Surgery, Gustave Roussy, Cancer Center Villejuif, France.
authors.forename: Chafouny
authors.initials: C
authors.lastname: Mazouni
authors.affiliation: Center for Therapeutic Innovations in Oncology and Haematology (CITOH), APHP, Hôpital Saint-Louis, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tembo
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, 75475 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Espié
authors.affiliation: Institut Curie, PSL Research University, Translational Research Department, INSERM, U932 Immunity and Cancer, Residual Tumor & Response to Treatment Laboratory (RT2Lab), Paris, France; Department of Surgery, Institut Curie, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.affiliation: AP-HP, Hôpital Saint-Louis, Breast Disease Unit, University Paris Diderot, 75475 Paris, France; Center for Therapeutic Innovations in Oncology and Haematology (CITOH), APHP, Hôpital Saint-Louis, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marty
authors.affiliation: UMR 8081 'IR4M', Université Paris-Sud, 91400 Orsay, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.affiliation: Medical Oncology Department, Institut Curie, Saint Cloud, Paris, France; Université Paris Descartes, Sorbonne Paris Cite, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000068579:Celecoxib / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000068579:Celecoxib; D003520:Cyclophosphamide; D015251:Epirubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: Breast cancer; Celecoxib; Long-term outcome; Neoadjuvant chemotherapy; Trastuzumab