First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial.

J. Cuzick, J. F. Forbes, I. Sestak, S. Cawthorn, H. Hamed, K. Holli, A. Howell, Fiona Jane Gilbert, IBIS Investigators

Research output: Contribution to journalArticle

640 Citations (Scopus)

Abstract

Background Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results. The overall evidence supports a reduction in the risk of breast cancer, but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear.

Methods We undertook a double-blind placebo-controlled randomised trial of tamoxifen, 20 mg/day for 5 years, in 7152 women aged 35-70 years, who were at increased risk of breast cancer. The primary outcome measure was the frequency of breast cancer (including ductal carcinoma in situ). Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography.

Findings After median follow-up of 50 months (IQR 32-67), 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group (risk reduction 32% [95% Cl 8-50]; p=0.013). Age, degree of risk, and use of hormone-replacement therapy did not affect the reduction. Endometrial cancer was non-significantly increased (11 vs 5; p=0.2) and thromboembolic events were significantly increased with tamoxifen (43 vs 17; odds ratio 2.5 [1.5-4.4], p=0.001), particularly after surgery. There was a significant excess of deaths from all causes in the tamoxifen group (25 vs 11, p=0.028).

Interpretation Prophylactic tamoxifen reduces the risk of breast cancer by about a third. Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation. Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease. The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen. The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear, and continued follow-up of the current trials is essential.

Original languageEnglish
Pages (from-to)817-824
Number of pages7
JournalThe Lancet
Volume360
Publication statusPublished - 2002

Keywords

  • POSTMENOPAUSAL WOMEN
  • TAMOXIFEN
  • RISK
  • REPLACEMENT
  • THERAPY
  • DISEASE
  • HEART

Cite this

Cuzick, J., Forbes, J. F., Sestak, I., Cawthorn, S., Hamed, H., Holli, K., ... IBIS Investigators (2002). First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. The Lancet, 360, 817-824.

First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. / Cuzick, J.; Forbes, J. F.; Sestak, I.; Cawthorn, S.; Hamed, H.; Holli, K.; Howell, A.; Gilbert, Fiona Jane; IBIS Investigators.

In: The Lancet, Vol. 360, 2002, p. 817-824.

Research output: Contribution to journalArticle

Cuzick, J, Forbes, JF, Sestak, I, Cawthorn, S, Hamed, H, Holli, K, Howell, A, Gilbert, FJ & IBIS Investigators 2002, 'First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial.', The Lancet, vol. 360, pp. 817-824.
Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. The Lancet. 2002;360:817-824.
Cuzick, J. ; Forbes, J. F. ; Sestak, I. ; Cawthorn, S. ; Hamed, H. ; Holli, K. ; Howell, A. ; Gilbert, Fiona Jane ; IBIS Investigators. / First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. In: The Lancet. 2002 ; Vol. 360. pp. 817-824.
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abstract = "Background Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results. The overall evidence supports a reduction in the risk of breast cancer, but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear.Methods We undertook a double-blind placebo-controlled randomised trial of tamoxifen, 20 mg/day for 5 years, in 7152 women aged 35-70 years, who were at increased risk of breast cancer. The primary outcome measure was the frequency of breast cancer (including ductal carcinoma in situ). Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography.Findings After median follow-up of 50 months (IQR 32-67), 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group (risk reduction 32{\%} [95{\%} Cl 8-50]; p=0.013). Age, degree of risk, and use of hormone-replacement therapy did not affect the reduction. Endometrial cancer was non-significantly increased (11 vs 5; p=0.2) and thromboembolic events were significantly increased with tamoxifen (43 vs 17; odds ratio 2.5 [1.5-4.4], p=0.001), particularly after surgery. There was a significant excess of deaths from all causes in the tamoxifen group (25 vs 11, p=0.028).Interpretation Prophylactic tamoxifen reduces the risk of breast cancer by about a third. Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation. Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease. The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen. The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear, and continued follow-up of the current trials is essential.",
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T1 - First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial.

AU - Cuzick, J.

AU - Forbes, J. F.

AU - Sestak, I.

AU - Cawthorn, S.

AU - Hamed, H.

AU - Holli, K.

AU - Howell, A.

AU - Gilbert, Fiona Jane

AU - IBIS Investigators

PY - 2002

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N2 - Background Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results. The overall evidence supports a reduction in the risk of breast cancer, but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear.Methods We undertook a double-blind placebo-controlled randomised trial of tamoxifen, 20 mg/day for 5 years, in 7152 women aged 35-70 years, who were at increased risk of breast cancer. The primary outcome measure was the frequency of breast cancer (including ductal carcinoma in situ). Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography.Findings After median follow-up of 50 months (IQR 32-67), 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group (risk reduction 32% [95% Cl 8-50]; p=0.013). Age, degree of risk, and use of hormone-replacement therapy did not affect the reduction. Endometrial cancer was non-significantly increased (11 vs 5; p=0.2) and thromboembolic events were significantly increased with tamoxifen (43 vs 17; odds ratio 2.5 [1.5-4.4], p=0.001), particularly after surgery. There was a significant excess of deaths from all causes in the tamoxifen group (25 vs 11, p=0.028).Interpretation Prophylactic tamoxifen reduces the risk of breast cancer by about a third. Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation. Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease. The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen. The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear, and continued follow-up of the current trials is essential.

AB - Background Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results. The overall evidence supports a reduction in the risk of breast cancer, but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear.Methods We undertook a double-blind placebo-controlled randomised trial of tamoxifen, 20 mg/day for 5 years, in 7152 women aged 35-70 years, who were at increased risk of breast cancer. The primary outcome measure was the frequency of breast cancer (including ductal carcinoma in situ). Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography.Findings After median follow-up of 50 months (IQR 32-67), 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group (risk reduction 32% [95% Cl 8-50]; p=0.013). Age, degree of risk, and use of hormone-replacement therapy did not affect the reduction. Endometrial cancer was non-significantly increased (11 vs 5; p=0.2) and thromboembolic events were significantly increased with tamoxifen (43 vs 17; odds ratio 2.5 [1.5-4.4], p=0.001), particularly after surgery. There was a significant excess of deaths from all causes in the tamoxifen group (25 vs 11, p=0.028).Interpretation Prophylactic tamoxifen reduces the risk of breast cancer by about a third. Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation. Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease. The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen. The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear, and continued follow-up of the current trials is essential.

KW - POSTMENOPAUSAL WOMEN

KW - TAMOXIFEN

KW - RISK

KW - REPLACEMENT

KW - THERAPY

KW - DISEASE

KW - HEART

M3 - Article

VL - 360

SP - 817

EP - 824

JO - The Lancet

JF - The Lancet

SN - 0140-6736

ER -