Italian randomized trial among women with hysterectomy: Tamoxifen and hormone-dependent breast cancer in high-risk women

Umberto Veronesi, Patrick Maisonneuve, Nicole Rotmensz, Alberto Costa, Virgilio Sachhini, Roberto Travaglini, Giuseppe D'Aiuto, Francesco Lovison, Giacomo Gucciardo, Maria Grazia Muraca, Maria Antonietta Pizzichetta, Serafino Conforti, Andrea Decensi, Chris Robertson, Peter Boyle

Research output: Contribution to journalArticlepeer-review


Tamoxifen improves outcome in women with breast cancer and reduces the incidence of estrogen receptor-positive (ER+) breast tumors in prevention trials. Tamoxifen use is associated with an increased risk of potentially serious adverse events, principally endometrial cancer and venous thromboembolic events and, therefore, detailed knowledge of the effects of tamoxifen is important. With more cases of breast cancer being found as the follow-up time increases, it is now possible to perform more detailed analysis of the Italian Randomized Trial of Tamoxifen. Women with hysterectomy (N = 5408) were randomly assigned to receive 20 mg tamoxifen per day (N = 2700) or placebo (N = 2708). After a median of 81.2 months of follow-up, 79 case subjects (34 in the tamoxifen arm and 45 in the placebo arm) were diagnosed with breast cancer. We were able to identify a group of women at increased risk of ER+ breast cancers (high-risk group) on the basis of baseline as well as reproductive and hormonal characteristics (height, age at menarche, parity, age at first birth, and oophorectomy). Tamoxifen administered to women in the high-risk group showed statistically significantly reduced incidence of breast cancer (tamoxifen, 3 and placebo, 15; P = .003), but no such effect was seen in the low-risk group (tamoxifen, 31 and placebo, 30; P = .89). The positive effect of tamoxifen on breast cancer among high-risk women is most marked for ER+ tumors (tamoxifen, 1 and placebo, 11; P = .002). Chemoprevention of breast cancer with tamoxifen appears to be effective in women at high risk of ER+ tumors but not among women at low risk, who may well be protected naturally by late age at menarche or early first pregnancy, or artificially by removal of the ovaries. Tamoxifen could be offered as a preventive agent to women identified at high-risk of breast cancer because of hormone-related risk factors. Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalJournal of the National Cancer Institute
Issue number2
Publication statusPublished - Jan 15 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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