title: Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.
abstract: BACKGROUND
  Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer.
  
  
  METHODS
  In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials.
  
  
  RESULTS
  After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women.
  
  
  CONCLUSIONS
  In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Olivia
authors.initials: O
authors.lastname: Pagani
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Walley
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: István
authors.initials: I
authors.lastname: Láng
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gomez
authors.forename: Carlo
authors.initials: C
authors.lastname: Tondini
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Eva
authors.initials: E
authors.lastname: Ciruelos
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.forename: Hervé R
authors.initials: HR
authors.lastname: Bonnefoi
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinotti
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.forename: Diana
authors.initials: D
authors.lastname: Crivellari
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruhstaller
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Manuela
authors.initials: M
authors.lastname: Rabaglio-Poretti
authors.forename: Rudolf
authors.initials: R
authors.lastname: Maibach
authors.forename: Barbara
authors.initials: B
authors.lastname: Ruepp
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Jürg
authors.initials: J
authors.lastname: Bernhard
authors.forename: Weixiu
authors.initials: W
authors.lastname: Luo
authors.forename: Karin
authors.initials: K
authors.lastname: Ribi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Francis
mesh_terms: D000328:Adult; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004958:Estradiol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008408:Mastectomy; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced; D017697:Premenopause; D011788:Quality of Life; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D017329:Triptorelin Pamoate / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D017329:Triptorelin Pamoate; D013629:Tamoxifen; D004958:Estradiol; C056516:exemestane