title: Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
abstract: OBJECTIVE
  To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers.
  
  
  METHODS
  Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up.
  
  
  RESULTS
  Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases).
  
  
  CONCLUSIONS
  This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
authors.affiliation: Division of Cancer Medicine, Peter MacCallum Cancer Centre, Australia. kelly.philips@petermac.org
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Matti A
authors.initials: MA
authors.lastname: Rookus
authors.forename: Mary B
authors.initials: MB
authors.lastname: Daly
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Susan
authors.initials: S
authors.lastname: Peock
authors.forename: Debra
authors.initials: D
authors.lastname: Frost
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Steve
authors.initials: S
authors.lastname: Ellis
authors.forename: Michael L
authors.initials: ML
authors.lastname: Friedlander
authors.forename: Saundra S
authors.initials: SS
authors.lastname: Buys
authors.forename: Nadine
authors.initials: N
authors.lastname: Andrieu
authors.forename: Catherine
authors.initials: C
authors.lastname: Noguès
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Valérie
authors.initials: V
authors.lastname: Bonadona
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
authors.forename: Sue Anne
authors.initials: SA
authors.lastname: McLachlan
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldes
authors.forename: Prue C
authors.initials: PC
authors.lastname: Weideman
authors.forename: Irene L
authors.initials: IL
authors.lastname: Andrulis
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Kate
authors.initials: K
authors.lastname: Birch
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Håkan L
authors.initials: HL
authors.lastname: Olsson
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Edith
authors.initials: E
authors.lastname: Olah
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gerdes
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen
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