Reduction in Breast Density Predicts Potential Benefit of Tamoxifen

Reduction in breast density appears to be a strong indicator of a woman’s response to tamoxifen, an agent used to decrease breast cancer risk. Increased breast density is the leading risk factor for breast cancer, apart from age.

At the CTRC-AACR San Antonio Breast Cancer Symposium, the British researchers said that if their findings are validated in follow-up studies, women at risk for developing breast cancer should have a baseline mammogram before starting use of tamoxifen, and then a follow-up scan a year or two later to monitor breast density.

If there is a reduction, the agent is having an effect; if density is the same, it may not be a beneficial drug for the individual woman, said the study’s lead investigator, Jack Cuzick, Ph.D., head of the Cancer Research UK Centre for Epidemiology, Mathematics and Statistics in London.

“It is important to find a way to predict who will respond to tamoxifen, and changes in breast density may constitute an early indicator of benefit,” said Cuzick. “This is important to know because other preventive options now exist or are being tested.” Cuzick led the International Breast Intervention Study I (IBIS-I), a trial of tamoxifen for breast cancer prevention that involved more than 7,000 participants. Results of the study found the agent reduces the risk of estrogen-positive (ER) breast cancer by 30 to 40 percent among women at high risk. During that study, researchers collected baseline mammograms, as well as mammograms at 18, 36, and 54 months to check for breast cancer development. Based on analysis of these mammograms, Cuzick and his colleagues later found a strong correlation between reduction of breast density in women who use tamoxifen and lowered breast cancer risk.

In this study, the investigators examined a subpopulation of the IBIS-I participants (120 women who developed breast cancer and 943 who didn’t), to see if their mammograms changed over time and if tamoxifen treatment reduced breast density. They also looked at changes in other variables, such as hormone status, body weight and familial factors. They found that only change in mammographic density predicted reduction of risk for ER-positive breast cancer.

For the 46 percent of women in the tamoxifen-treatment group whose breast density was reduced by 10 percent or more, the risk of breast cancer was reduced by 52 percent relative to the control group (women who did not develop breast cancer). Conversely, the 54 percent of women whose density was not reduced by 10 percent only had a non-significant, 8 percent reduction in breast cancer risk. The findings suggest that the impact of tamoxifen on risk reduction is predictable by changes it induces on breast density after 12 to 18 months of treatment, Cuzick said.

For more information:
Cuzick J, Warwick J, Pinney L, Warren R, Cawthorn S, et al. Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1. Abstract 61; SABCS, December 10-14, 2008.