Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

A case-control study

Steven A. Narod, Jean Sébastien Brunet, Parviz Ghadirian, Mark Robson, Ketil Heimdal, Susan L. Neuhausen, Dominique Stoppa-Lyonnet, Caryn Lerman, Barbara Pasini, Patricia De Los Rios, Barbara Weber, Henry T. Lynch

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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.

Original languageEnglish
Pages (from-to)1876-1881
Number of pages6
JournalThe Lancet
Volume356
Issue number9245
StatePublished - Dec 2 2000

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Tamoxifen
Case-Control Studies
Breast Neoplasms
Mutation
Ovariectomy
Odds Ratio
BRCA2 Gene
BRCA1 Gene
Second Primary Neoplasms
Risk Reduction Behavior
Neoplasms
Interviews
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Narod, S. A., Brunet, J. S., Ghadirian, P., Robson, M., Heimdal, K., Neuhausen, S. L., ... Lynch, H. T. (2000). Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study. The Lancet, 356(9245), 1876-1881.

Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers : A case-control study. / Narod, Steven A.; Brunet, Jean Sébastien; Ghadirian, Parviz; Robson, Mark; Heimdal, Ketil; Neuhausen, Susan L.; Stoppa-Lyonnet, Dominique; Lerman, Caryn; Pasini, Barbara; De Los Rios, Patricia; Weber, Barbara; Lynch, Henry T.

In: The Lancet, Vol. 356, No. 9245, 02.12.2000, p. 1876-1881.

Research output: Contribution to journalArticle

Narod, SA, Brunet, JS, Ghadirian, P, Robson, M, Heimdal, K, Neuhausen, SL, Stoppa-Lyonnet, D, Lerman, C, Pasini, B, De Los Rios, P, Weber, B & Lynch, HT 2000, 'Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study', The Lancet, vol. 356, no. 9245, pp. 1876-1881.
Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, Neuhausen SL et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study. The Lancet. 2000 Dec 2;356(9245):1876-1881.
Narod, Steven A. ; Brunet, Jean Sébastien ; Ghadirian, Parviz ; Robson, Mark ; Heimdal, Ketil ; Neuhausen, Susan L. ; Stoppa-Lyonnet, Dominique ; Lerman, Caryn ; Pasini, Barbara ; De Los Rios, Patricia ; Weber, Barbara ; Lynch, Henry T. / Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers : A case-control study. In: The Lancet. 2000 ; Vol. 356, No. 9245. pp. 1876-1881.
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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.",
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T1 - Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

T2 - A case-control study

AU - Narod, Steven A.

AU - Brunet, Jean Sébastien

AU - Ghadirian, Parviz

AU - Robson, Mark

AU - Heimdal, Ketil

AU - Neuhausen, Susan L.

AU - Stoppa-Lyonnet, Dominique

AU - Lerman, Caryn

AU - Pasini, Barbara

AU - De Los Rios, Patricia

AU - Weber, Barbara

AU - Lynch, Henry T.

PY - 2000/12/2

Y1 - 2000/12/2

N2 - 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.

AB - 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.

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