title: A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.
abstract: BACKGROUND
  Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse.
  
  
  METHODS
  We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival.
  
  
  RESULTS
  Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04).
  
  
  CONCLUSIONS
  Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
authors.affiliation: Department of Cancer Medicine, Imperial College and Charing Cross Hospital, London, United Kingdom.
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
authors.forename: Emma
authors.initials: E
authors.lastname: Hall
authors.forename: Lorna J
authors.initials: LJ
authors.lastname: Gibson
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Thierry
authors.initials: T
authors.lastname: Delozier
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Jones
authors.forename: Isabel
authors.initials: I
authors.lastname: Alvarez
authors.forename: Gianfilippo
authors.initials: G
authors.lastname: Bertelli
authors.forename: Olaf
authors.initials: O
authors.lastname: Ortmann
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: David
authors.initials: D
authors.lastname: Dodwell
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Fallowfield
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mickiewicz
authors.forename: Jorn
authors.initials: J
authors.lastname: Andersen
authors.forename: Per E
authors.initials: PE
authors.lastname: Lønning
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cocconi
authors.forename: Alan
authors.initials: A
authors.lastname: Stewart
authors.forename: Nick
authors.initials: N
authors.lastname: Stuart
authors.forename: Claire F
authors.initials: CF
authors.lastname: Snowdon
authors.forename: Marina
authors.initials: M
authors.lastname: Carpentieri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Massimini
authors.forename: Judith M
authors.initials: JM
authors.lastname: Bliss
authors.forename: Cornelius
authors.initials: C
authors.lastname: van de Velde
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C056516:exemestane