title: Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial.
abstract: BACKGROUND
  Among cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)-positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown.
  
  
  OBJECTIVE
  To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations.
  
  
  METHODS
  Genomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999).
  
  
  METHODS
  Among women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo.
  
  
  RESULTS
  Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1 or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive.
  
  
  CONCLUSIONS
  Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown.
authors.affiliation: University of Washington, Seattle, WA 98195, USA. mcking@u.washington.edu
authors.forename: M C
authors.initials: MC
authors.lastname: King
authors.forename: S
authors.initials: S
authors.lastname: Wieand
authors.forename: K
authors.initials: K
authors.lastname: Hale
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Walsh
authors.forename: K
authors.initials: K
authors.lastname: Owens
authors.forename: J
authors.initials: J
authors.lastname: Tait
authors.forename: L
authors.initials: L
authors.lastname: Ford
authors.forename: B K
authors.initials: BK
authors.lastname: Dunn
authors.forename: J
authors.initials: J
authors.lastname: Costantino
authors.forename: L
authors.initials: L
authors.lastname: Wickerham
authors.forename: N
authors.initials: N
authors.lastname: Wolmark
authors.forename: B
authors.initials: B
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D004252:DNA Mutational Analysis; D004311:Double-Blind Method; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D011960:Receptors, Estrogen; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen