SAN ANTONIO—Tamoxifen significantly reduces breast cancer incidence among women at high risk, according to a long-term follow-up analysis of participants in the International Breast Cancer Intervention Study-I (IBIS-I) trial. The findings were presented at the 2014 San Antonio Breast Cancer Symposium.

“We found that the reduction in breast cancer incidence remains strong and unabated for 20 years,” reported lead study author said Jack Cuzick, PhD, John Snow Professor of Epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University of London, England.  “After 20 years follow-up, results show a clear long-term benefit of 5 years of tamoxifen for preventing breast cancer” of 7.8% versus 12.3%.

“Estrogen receptor [ER]–positive invasive cancer, which represents two-thirds of all breast cancers, was reduced by 35%,” he said.

“Benefits were higher among women who were not on hormone replacement therapy (HRT) during their time on-trial (P = 0.04)”, he noted.

“The study showed clear benefits of tamoxifen in reducing breast cancer incidence, but there is uncertainty with respect to the mortality impact,” he cautioned.

The aromatase inhibitors anastrozole or exemestane “are probably better alternatives, both in terms of greater effectiveness and better side-effect profiles,” for postmenopausal women, Dr. Cuzick noted. “But for premenopausal women, tamoxifen remains the only choice and it is a good one.”

IBIS-I was undertaken to assess the long-term risks and benefits of tamoxifen as a cancer prevention measure among women at high risk for breast cancer.

A total of 7,154 women age 35 to 70 years with an increased risk for breast cancer enrolled in the trial and were randomly assigned to receive tamoxifen (20 mg daily; n=3,579) or placebo (n=3,575) for 5 years.

At a median follow-up of 16 years, the cumulative incidences for all breast cancers were 251 versus 350 for tamoxifen versus placebo (hazard ratio [HR]: 0.71; 95% CI: 0.60-0.83), and the cumulative incidences for invasive ER-positive breast cancers were 160 versus 238 (HR: 0.65; 95% CI: 0.54-0.81), he reported.

Patients in the tamoxifen group had nine more endometrial cancer diagnoses than those in the placebo group (odds ratio [OR]: 1.45) and 32 more diagnoses of rarely lethal nonmelanoma skin cancers (OR: 1.39), Dr. Cuzick noted—but these were not statistically significant differences.

“Breast cancer is the epidemic of our century,” he concluded. “We need to do more than just treat breast cancer—we need to find ways to bring incidence down.”

The study was funded by Cancer Research UK and AstraZeneca; Dr. Cuzick reported that he is an ad hoc speaker for AstraZeneca.


  1. Cuzick J, Sestak I, Cawthorn S et al. S3-07. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.