NSABP Researchers Report on the Tamoxifen Breast Cancer Prevention Trial

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 prevention trial.

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 tamoxifen therapy.

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 trial’s 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.

Tamoxifen’s 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 woman’s 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.