After a median of 16 years of following women at high risk for breast cancer, the International Breast Cancer Intervention Study-I (IBIS-I) trial found that tamoxifen significantly decreased the incidence of all breast cancers, according to data presented at the 2014 San Antonio Breast Cancer Symposium.

“The International Breast Cancer Intervention Study-I was designed to investigate the long-term risks and benefits of taking tamoxifen to prevent breast cancer in women at high risk for developing the disease,” said Jack Cuzick, PhD, John Snow professor of epidemiology at Wolfson Institute of Preventive Medicine at Queen Mary University of London in the United Kingdom.

“We found that the reduction in breast cancer incidence remains strong and unabated for 20 years,” added Cuzick. “There are concerns related to endometrial cancer mortality and development of estrogen receptor [ER]-negative cancers but they are statistically nonsignificant, and could be chance observations.

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

Of the 7,154 pre- and postmenopausal women recruited to the IBIS-I trial, 3,579 were randomly assigned to receive daily 20 mg tamoxifen for 5 years, and 3,575 were randomly assigned to receive a matching placebo for 5 years. The women were ages 35 to 70 years with an increased risk for breast cancer, primarily due to a family history of the disease.

The primary end point of this study was the occurrence of noninvasive or invasive breast cancer, and the secondary end points included overall mortality, other cancers, and breast cancer-specific mortality.

During a median of 16 years of follow-up, 246 women from the tamoxifen group and 343 from the placebo group developed breast cancers. There was a 29% reduction in breast cancer rates among women from the tamoxifen group. The rates of ER-positive breast cancer were reduced by 35%, but no effect was seen for ER-negative breast cancers.

Larger benefits were seen for women who did not take hormone replacement therapy (HRT) during the trial: 45% reduction for ER-positive breast cancer and 38% reduction for all breast cancers in noncurrent HRT users.

No differences were seen in breast cancer-related mortality rates between the two groups. However, among women who took tamoxifen, there was a nonsignificant increase in all-cause mortality, but this was smaller than seen in the 96-month follow up report, according to Cuzick.

There was a nonsignificant increase in other cancers overall, with increases in endometrial cancer and nonmelanoma skin cancer, and decreases in colorectal cancer.

“While the durability of the breast cancer incidence reduction is an important finding, some uncertainties still remain about mortality effects,” said Cuzick.

This study was funded by Cancer Research UK and AstraZeneca. Cuzick is an ad hoc speaker for AstraZeneca.