SAN ANTONIO—Tamoxifen (Nolvadex) reduces the risk of contralateral breast cancer to a degree similar to its effect on primary breast cancer, according to an analysis of data from National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials.
Patients treated with tamoxifen(Drug information on tamoxifen) had about a 40% reduction in the risk of contralateral breast cancer. Similar benefits were observed with respect to invasive and noninvasive contralateral cancers, and the benefits persist for up to 10 years.
“The role of tamoxifen in breast cancer continues to be defined. The benefits are clear in ER-positive patients,” said Eleftherios (Terry) Mamounas, MD, of Mt. Sinai Medical Center, Cleveland, who presented the study on behalf of the NSABP. “However, the role of tamoxifen in ER-negative patients has not yet been established,” he said.
Analysis of Nine NSABP Trials
The findings came from an analysis of nine recent NSABP breast cancer therapy trials. The results were compared with those from the NSABP Breast Cancer Prevention Trial (BCPT), which showed a 45% reduction in the risk of primary breast cancer in high-risk patients treated with tamoxifen.
“History of breast cancer is a major risk factor for subsequent contralateral breast cancer,” Dr. Mamounas said. “We wanted to assess the incidence of contralateral breast cancer in recent NSABP adjuvant trials and compare the results with those from the prevention trial. We also wanted to examine factors that influence the risk of contralateral breast cancer, including tamoxifen use.”
In the BCPT, 6,700 patients randomized to placebo had an annual breast cancer incidence of 9 per 1,000 women, compared with 4.9 per 1,000 women treated with tamoxifen. The 5-year breast cancer incidence per 1,000 women was 44.3 with placebo and 24.7 in the tamoxifen group. Benefits were similar with respect to invasive and noninvasive cancer.
Dr. Mamounas and his colleagues reviewed data from NSABP trials B-13 to B-20 and B-22. These trials involved patients with node-negative, node-positive, or intraductal cancer. Collectively, the trials enrolled more than 15,000 patients.
The incidence of contralateral breast cancer averaged 7.4 per 1,000 women per year among patients who did not receive tamoxifen in the treatment trials. That compared with a rate of 4.4 among those who did receive tamoxifen. The 5-year cumulative incidence was 29.3 per 1,000 women among those who did not receive tamoxifen vs 16.9 in the tamoxifen-treated patients.
In reviewing factors that might influence the risk of contralateral breast cancer, the investigators found no significant effect associated with chemotherapy use, lymph node status, or receptor status. There was a trend toward increased rate of contralateral breast cancer in women under 40 years of age.
ER-Negative Benefits Questioned
The benefits of tamoxifen therapy in ER-negative breast cancer patients remain unproven, and recent data suggest no benefit, commented C. Kent Osborne, MD, director of medical oncology, University of Texas Health Science Center at San Antonio.
Dr. Osborne noted that tamoxifen has not been shown to improve overall survival or disease-free survival in receptor-negative patients. Additionally, he said, a randomized, prospective trial reported last year at the American Society of Clinical Oncology (ASCO) meeting suggested “a trend, a pretty good trend, toward tamoxifen being inferior to no tamoxifen in the ER-negative group.”
Longer Follow-up Needed
At this point, Dr. Osborne said, “I would be a little reluctant to recommend tamoxifen in ER-negative patients until this issue is settled with longer follow-up. It may turn out that tamoxifen does reduce contralateral breast cancer in this population of patients, but it has not yet been shown.”
