Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study Journal Article


Authors: Narod, S. A.; Brunet, J. S.; Ghadirian, P.; Robson, M.; Heimdal, K.; Neuhausen, S. L.; Stoppa-Lyonnet, D.; Lerman, C.; Pasini, B.; De Los Rios, P.; Weber, B.; Lynch, H.; for the Hereditary Breast Cancer Clinical Study Group
Contributors: Offit, K.; Levine, D.; Anderson, M. D.; Mills, G.
Article Title: Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study
Abstract: Background: Women with a mutation in BRCA1 or BRCA2 have a high risk of developing breast cancer and of contralateral cancer after the initial diagnosis of breast cancer. Tamoxifen protects against contralateral breast cancer in the general population, but whether it protects against contralateral breast cancer in BRCA1 or BRCA2 mutation carriers is not known. Methods: We compared 209 women with bilateral breast cancer and BRCA1 or BRCA2 mutation (bilateral-disease cases), with 384 women with unilateral disease and BRCA1 or BRCA2 mutation (controls) in a matched case-control study. Age and age at diagnosis of breast cancer (range 24-74 years) were much the same in bilateral-disease cases and controls, and both groups had been followed up for the same time for a second primary breast cancer. History of tamoxifen use for first breast cancer was obtained by interview, or by self-administered questionnaire. Findings: The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0-50 (95% Cl 0.28-0.89). Tamoxifen protected against contralateral breast cancer for carriers of BRCA1 mutations (odds ratio 0.38, 95% Cl 0-19-0-74) and for those with BRCA2 mutations (0.63, 0-20-1-50). In women who used tamoxifen for 2-4 years, the risk of contralateral breast cancer was reduced by 75%. A reduction in risk of contralateral cancer was also seen with oophorectomy (0.42, 0-22-0.83) and with chemotherapy (0 40, 0-26-0.60). Interpretation: Tamoxifen use reduces the risk of contralateral breast cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene. The protective effect of tamoxifen seems independent of that of oophorectomy.
Keywords: adult; controlled study; aged; middle aged; gene mutation; major clinical study; mutation; case-control studies; clinical trial; cancer risk; drug efficacy; cancer prevention; controlled clinical trial; breast cancer; ovariectomy; neoplasm proteins; odds ratio; risk factors; age factors; breast neoplasms; brca1 protein; brca2 protein; time factors; questionnaires; transcription factors; oncogene; tamoxifen; neoplasms, second primary; antineoplastic agents, hormonal; humans; human; female; priority journal; article
Journal Title: Lancet
Volume: 356
Issue: 9245
ISSN: 0140-6736
Publisher: Elsevier Science, Inc.  
Date Published: 2000-12-02
Start Page: 1876
End Page: 1881
Language: English
PUBMED: 11130383
PROVIDER: scopus
DOI: 10.1016/S0140-6736(00)03258-X
DOI/URL:
Notes: Export Date: 18 November 2015 -- Source: Scopus
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  1. Kenneth Offit
    788 Offit
  2. Mark E Robson
    676 Robson
  3. Deborah A Levine
    5 Levine