title: Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials.
abstract: BACKGROUND
  Several trials have been done to assess treatment of premenopausal breast cancer with luteinising-hormone-releasing hormone (LHRH) agonists, but results have been inconclusive, especially for patients with hormone-receptor-positive cancer.
  
  
  METHODS
  We collected individual patients' data from published trials and did analyses focused on women with tumours positive for oestrogen receptor, progesterone receptor, or both. The main endpoints were recurrence and death after recurrence.
  
  
  RESULTS
  We obtained data for 11 906 premenopausal women with early breast cancer randomised in 16 trials. When used as the only systemic adjuvant treatment, LHRH agonists did not significantly reduce recurrence (28.4% relative reduction, 95% CI consistent with 50.5% reduction to 3.5% increase, p=0.08) or death after recurrence (17.8%, 52.8% reduction to 42.9% increase, p=0.49) in hormone-receptor-positive cancers. Addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced recurrence by 12.7% (2.4-21.9, p=0.02); and death after recurrence by 15.1% (1.8-26.7, p=0.03). LHRH agonists showed similar efficacy to chemotherapy (recurrence 3.9% increase, 7.7% reduction to 17.0% increase; death after recurrence 6.7% reduction, 20.7% reduction to 9.6% increase; both not significant). No trials had assessed an LHRH agonist versus chemotherapy with tamoxifen in both arms. LHRH agonists were ineffective in hormone-receptor-negative tumours.
  
  
  CONCLUSIONS
  LHRH agonists provide an additional class of agents for treatment of premenopausal women with hormone-receptor-positive breast cancer. Optimum duration of use is unknown.
authors.affiliation: Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. jack.cuzick@cancer.org.uk
authors.forename: J
authors.initials: J
authors.lastname: Cuzick
authors.forename: L
authors.initials: L
authors.lastname: Ambroisine
authors.forename: N
authors.initials: N
authors.lastname: Davidson
authors.forename: R
authors.initials: R
authors.lastname: Jakesz
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
authors.forename: M
authors.initials: M
authors.lastname: Regan
authors.forename: R
authors.initials: R
authors.lastname: Sainsbury
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004347:Drug Interactions; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control; D017697:Premenopause; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone