제  목 : Interim Reports Published on Two European Breast Cancer
  일  자 : 1998년 07월
  제공처 : Internet

   Interim Reports Published on Two European Breast Cancer Prevention Trials
   =========================================================================

   In two articles published today in the journal Lancet, European
   scientists reported that they found no significant difference in the
   number of breast cancer cases between women taking tamoxifen and women
   given a placebo. The failure to detect a difference between these groups
   is in contrast to the approximately 45 percent reduction in breast cancer
   incidence in women taking tamoxifen in the Breast Cancer Prevention Trial
   (BCPT). The BCPT results were announced in April of this year by the
   National Cancer Institute (NCI) and the National Surgical Adjuvant Breast
   and Bowel Project (NSABP), a Pittsburgh-based research network supported
   by NCI. The European studies that are the subject of the new articles are
   smaller in size than the BCPT, and there are differences in the
   populations studied that may account for the different conclusions.

 1. What are the findings of the European studies?

      Preliminary reports from the two European trials of
      tamoxifen did not find a statistically significant
      difference in the number of breast cancer cases
      between women taking tamoxifen and those taking a
      placebo.

 2. What are the findings of the BCPT?

      The BCPT found a highly significant reduction in
      breast cancer incidence in women at
      greater-than-average risk of breast cancer. The group
      of women taking tamoxifen in this study had 45
      percent fewer cases of breast cancer than the group
      taking a placebo. The BCPT also documented certain
      serious side effects of tamoxifen, most notably
      vascular events and endometrial cancer.

 3. Are there studies in addition to BCPT that indicate
 that tamoxifen can prevent breast cancer?

      The BCPT was based on earlier observations on the
      effects of tamoxifen in women who already had breast
      cancer. It was noted that the women who took
      tamoxifen had a reduced incidence of new breast
      cancers in the opposite breast. This observation
      formed the basis for the BCPT, which has confirmed
      that tamoxifen can prevent breast cancer in healthy
      women at elevated risk.

 4. What features of the European studies might account
 for the differences with the BCPT?

      The European studies were of smaller size than BCPT.
      Included in the study in the United Kingdom were
      2,471 women, and 5,408 participated in the Italian
      study. By comparison, the BCPT included 13,388 women.
      BCPT included women with greater-than-average risk
      whereas the European studies involved women at lower
      risk than those in the BCPT. Another difference in
      the studies involved the use of estrogen hormone
      replacement therapy among a significant fraction of
      the participants in the European studies.

 5. How may the number of participants influence the
 findings of the studies?

      The number of participants in prevention trials is a
      major determinant of the likelihood of reliably
      detecting any differences that may exist between the
      tamoxifen and placebo groups. The larger the groups
      involved, the more likely it is that true differences
      between the groups will be detected with high
      probability. In contrast, the smaller the number of
      participants the more likely it is that any
      differences seen may be due to chance alone, or that
      real differences might be missed. In the case of the
      BCPT that involved 13,388 participants, the 45
      percent reduction in breast cancer incidence seen
      with tamoxifen is highly statistically significant,
      and the chances of this size reduction in breast
      cancer being a "fluke" is less than 1 in 10,000.

 6. How might the differences in risk of breast cancer
 affect the findings of the studies?

      The biggest impact of a difference in the intrinsic
      risk of participants relates to the number of cases
      that are observed in the study. More cases occur in a
      study involving women at increased risk. The number
      of breast cancer cases in the BCPT was 329 (invasive
      plus non-invasive) whereas only 70 cases occurred in
      the UK study and only 41 in the Italian study. Of the
      329 cases in BCPT, 213 were in the placebo group and
      only 116 were in the tamoxifen group. This difference
      in case numbers between the groups is very
      significant. For the larger of the European studies,
      the numbers of cases were 36 and 34, respectively.
      For the smaller of the two studies, the numbers of
      cases were 22 in the placebo group and 19 in the
      tamoxifen group. The larger number of cases in the
      BCPT provides more confidence that the observed
      differences are real.

 7. How might participants' use of estrogen hormone
 replacement therapy affect the findings of the European
 studies?

      Tamoxifen can interact with the same receptor on
      cells that binds estrogen. Consequently, there is a
      theoretical possibility that estrogen use may block
      the effect of tamoxifen. In the two European studies,
      14 percent or 42 percent of the participants were
      taking estrogen. In the BCPT, the use of estrogen was
      not permitted so that the effect of tamoxifen alone
      could be evaluated.


 8. Were the BCPT results released too early?

      No. An integral part of the BCPT was an independent
      Endpoint Review, Safety Monitoring, and Advisory
      Committee. At its regularly scheduled meeting in
      March of 1998, this committee concluded that the
      BCPT's primary question-whether tamoxifen can prevent
      breast cancer in women at greater-than-average
      risk-had been answered. It was concluded that the
      value of additional information that might be gained
      from continuing the study did not outweigh the
      benefits of making tamoxifen available to the
      participants in the placebo group and other women at
      increased risk of breast cancer. The NSABP and NCI
      decided to inform participants of the findings, and
      the trial results were made public in April.

 9. How should the new publications about tamoxifen
 affect a woman's decision of whether or not to use
 tamoxifen in preventing breast cancer?

      The NCI's confidence in the results of the BCPT
      showing that tamoxifen can reduce breast cancer in
      women at increased risk remains firm. A women
      considering tamoxifen should discuss with her
      physician both the potential benefits of tamoxifen
      based on her personal breast cancer risk profile as
      well as the potential side effects of tamoxifen. The
      weighing of potential benefits and potential side
      effects is a personal decision.

 10. What additional studies will be of value in
 assessing tamoxifen for prevention of breast cancer?

      The NCI is pleased that the European studies are
      continuing. The very features of the trials that may
      account for the differences with the conclusions of
      the BCPT may yield new information about tamoxifen
      and breast cancer. For example, the European studies
      may provide valuable data regarding tamoxifen use by
      women at lower risk as well as insights into the
      impact of estrogen hormone replacement on tamoxifen's
      effects. The BCPT has provided a foundation for
      additional studies. NCI and the NSABP will later this
      year begin recruitment for a head-to-head study
      comparing tamoxifen with raloxifene, a related
      compound.

   The NCI remains confident in the results of the BCPT, a study that
   included 13,388 women at greater-than-average risk for breast cancer. For
   women at increased risk of breast cancer, tamoxifen can reduce that risk.
   The decision of whether to use tamoxifen for prevention of breast cancer
   is an important and personal decision, and a woman should discuss both
   the benefits and the risks associated with tamoxifen use with her
   physician.