title: Adjuvant ovarian suppression in premenopausal breast cancer.
abstract: BACKGROUND
  Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.
  
  
  METHODS
  We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.
  
  
  RESULTS
  After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).
  
  
  CONCLUSIONS
  Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Francis
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: István
authors.initials: I
authors.lastname: Láng
authors.forename: Eva
authors.initials: E
authors.lastname: Ciruelos
authors.forename: Meritxell
authors.initials: M
authors.lastname: Bellet
authors.forename: Hervé R
authors.initials: HR
authors.lastname: Bonnefoi
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Climent
authors.forename: Gian Antonio
authors.initials: GA
authors.lastname: Da Prada
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Walley
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Pierre
authors.initials: P
authors.lastname: Kerbrat
authors.forename: Stefan
authors.initials: S
authors.lastname: Buchholz
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
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: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
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; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D017697:Premenopause; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013629:Tamoxifen; C056516:exemestane