title: Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis.
abstract: BACKGROUND
  Although in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS).
  
  
  METHODS
  Relevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016. The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method).
  
  
  RESULTS
  A total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643). No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529).
  
  
  CONCLUSIONS
  Our pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Poggio
authors.affiliation: Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ceppi
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, and l'Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.affiliation: Department of Internal Medicine, University of Genoa, Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Ugolini
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bighin
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Levaggi
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Giraudi
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Alonzo
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vaglica
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Blondeaux
authors.affiliation: Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Sertoli
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino - IST, Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pronzato
authors.affiliation: Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino - IST, Genova, Italy. Electronic address: lucia.delmastro@hsanmartino.it.
authors.forename: L
authors.initials: L
authors.lastname: Del Mastro
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D047072:Aromatase Inhibitors; D001952:Bridged-Ring Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D043823:Taxoids; C080625:taxane; C508053:ERBB2 protein, human
keywords: Adjuvant chemotherapy; Adjuvant endocrine therapy; Breast cancer; Hormone-receptor positive