title: Exemestane for breast-cancer prevention in postmenopausal women.
abstract: BACKGROUND
  Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer.
  
  
  METHODS
  In a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured.
  
  
  RESULTS
  A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P=0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P=0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P=0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths. Minimal quality-of-life differences were observed.
  
  
  CONCLUSIONS
  Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life. (Funded by Pfizer and others; NCIC CTG MAP.3 ClinicalTrials.gov number, NCT00083174.).
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. pgoss@partners.org
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: José E
authors.initials: JE
authors.lastname: Alés-Martínez
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cheung
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: John
authors.initials: J
authors.lastname: Robbins
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Sarto
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Fabian
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maunsell
authors.forename: Patricia
authors.initials: P
authors.lastname: Farmer
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gelmon
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Harriet
authors.initials: H
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000453:epidemiology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017698:Postmenopause; D011788:Quality of Life; D012307:Risk Factors
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; C056516:exemestane