Researchers from the Pittsburgh-based National Surgical Adjuvant
Breast and Bowel Project (NSABP) presented data on the Breast Cancer
Prevention Trial (BCPT) during a plenary session of the recent
American Society of Clinical Oncology (ASCO) national meeting and
confirmed their plan to begin a second, large-scale breast cancer
Breast Cancer Prevention Trial Data
D. Lawrence Wickerham, MD, associate chairperson of the NSABP,
presented data demonstrating that with an average follow-up of 3.6
years, tamoxifen (Nolvadex) reduced the incidence of invasive breast
cancer by 45% (85 cases in the tamoxifen group vs 154 cases in the
placebo group; P < .00001) and also, reduced the incidence of
non-invasive breast cancer (31 cases in the tamoxifen group vs 59
cases in the placebo group; P = .002).
Women in the trial were monitored closely with regular breast
examinations and mammograms. As a result, any breast cancer that did
develop was detected in its early stages.
Participants with a prior history of biopsy-proven atypical
hyperplasia of the breast, or lobular carcinoma in situ (a
non-invasive breast cancer), represented more than 15% of the women
in the trial. Both of these groups benefited substantially from
The side effects associated with tamoxifen use included an increased
risk of endometrial cancer, pulmonary embolism, and deep-vein
thrombosis. These side effects, however, did not occur more
frequently than researchers predicted at the trials inception.
The consent form used in the trial indicated that tamoxifen had
previously been linked to an increased risk of developing a second
cancer of the gastrointestinal tract or the liver, as well as other
liver toxicities. Data from the BCPT found no difference in the
incidence of these second cancers between the two groups.
Tamoxifens Benefits Continue
How long the benefit of tamoxifen lasts in the prevention of breast
cancer was also considered. "In the adjuvant setting, the
benefits of tamoxifen do not stop with the last pill. Data from a
previous NSABP treatment trial in women with early-stage breast
cancer demonstrate that the benefits of the first 5 years of
tamoxifen continue through 10 years. This is true for both recurrence
of the original cancer and reduction of opposite breast cancers,"
said Dr. Wickerham.
The previous NSABP B-14 trial examined the effect of tamoxifen in
node-negative, estrogen-receptor-positive women and was the precursor
for the BCPT. Results from B-14 demonstrated an almost 50% reduction
in opposite breast cancers during the first 5 years of tamoxifen
therapy. The benefits of tamoxifen in the adjuvant setting have been
confirmed in trials conducted around the world.
Tamoxifen vs Raloxifene Trial
"The NSABP Breast Cancer Prevention Trial represents the first
step in making the hope of breast cancer prevention a reality,"
said Dr. Wickerham. "Based on the evidence from this trial and a
thorough review of the preliminary data indicating that raloxifene
[Evista] may have similar preventive effects, with fewer potential
side effects, the NSABP has submitted a proposal to the NCI seeking
support to begin a clinical trial that would compare tamoxifen to
raloxifene in postmenopausal women at high risk for developing breast
cancer. This proposal has been approved by the NCI, and the trial is
scheduled to begin in the fall of 1998.
The proposed upcoming breast cancer prevention trial is designed as a
double-blind, randomized study in which 22,000 postmenopausal women
age 35 years or older will be assigned to take either tamoxifen (20
mg orally) or raloxifene (60 mg orally) for 5 years. Follow-up
examinations, including blood tests, a mammogram, physical
examination, and gynecologic examination, will be performed annually.
Eligible women must be at increased risk for developing breast
cancer. Risk status will be determined based on a computerized
calculation that will consider the following factors: age, family
history of breast cancer, whether a woman has any children and her
age at first delivery, the number of times a woman has had a breast
lump biopsied, especially if the tissue was shown to have a condition
known as atypical hyperplasia, and a womans age at her first
menstrual period. Women with a diagnosis of lobular carcinoma in situ
will also be eligible.
National Surgical Adjuvant Breast and Bowel Project researchers
throughout the United States, Canada, and Puerto Rico estimate that
over 300 institutions will participate in this trial. Women who would
like to receive more information about the upcoming trial can place
their name on a confidential mailing list. On the Internet, an
Interest Form is available at the NSABP homepage address (http://www.nsabp.pitt.edu).
By regular mail, send a letter or postcard with name, mailing
address, and a note specifying interest in future breast cancer
prevention trials to: NSABP, Box 21, Pittsburgh, PA 15261. The same
information may also be faxed to the NSABP at (412) 330-4664.