SAN ANTONIO -- A new 10-year follow-up from a landmark clinical trial of tamoxifen for breast cancer prevention indicates that the benefit continues strongly throughout the next half decade following completion of the standard 5 years of therapy, whereas adverse events are confined to the active treatment period.
"The risk-benefit ratio improves with longer follow-up. I think this is terribly important for the overall evaluation of tamoxifen in prevention. If you get the same benefit in the second 5 years as in the first 5 years without any of the side effects, the risk-benefit ratio is going to be at least twice as good as that currently computed based on just 5 years of data," Jack Cuzick, Ph.D., said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
He presented a 10-year update from the first International Breast Cancer Prevention Study (IBIS-I), in which 7,154 women at high risk for breast cancer were randomized to 5 years of daily tamoxifen or placebo.
Such a placebo-controlled trial could not be undertaken today for ethical reasons because tamoxifen is now approved as a breast cancer chemopreventive agent; however, at 10 years the IBIS-I participants still remain blinded as to their treatment arm.
The primary end point was the incidence of breast cancer, which at 10 years was 3.9% in the tamoxifen arm and 5.5% with placebo, for a highly significant 29% relative risk reduction. This result included a 38% reduction in ductal carcinoma in situ and a 27% decrease in invasive breast cancers. There were 87 estrogen receptor-positive invasive breast cancers in the tamoxifen group and 129 in controls, for a 34% relative risk reduction. As expected, tamoxifen had no effect on the rate of estrogen receptor-negative tumors, said Dr. Cuzick, the IBIS-I chairman and head of the center for epidemiology, mathematics, and statistics at Cancer Research UK, London.
Tamoxifen prevented tumors of all grades. Importantly, the risk reduction was as great in year 10 as in year 1.
"This strong late reduction in cancers is very strong evidence that we're not only preventing the early cancers, which could to some extent be a matter of holding cancers in check, but we're actually preventing new tumors, and that this preventive effect is very, very long-term indeed," added Dr. Cuzick, who is also the John Snow Professor of Epidemiology at the Wolfson Institute of Preventive Medicine at Queen Mary's, University of London.
There was a strong, albeit nonsignificant, trend for a greater reduction in invasive breast cancers with tamoxifen in the 48% of subjects who were premenopausal at entry. …