Lower breast density flags drug response.(NEWS)

SAN ANTONIO--A reduction in mammographic breast density after 12-18 months of tamoxifen use--prescribed for primary prevention of breast cancer--is an excellent early predictor of subsequent treatment efficacy, according to a new report from the landmark International Breast Intervention Study I (IBIS-I).

Women who showed at least a 10% decrease in breast density by visual assessment on routine mammography 12-18 months into their 5-year course of tamoxifen had a 63% reduction in breast cancers compared with placebo through 8 years of follow-up in IBIS-I, Jack Cuzick, Ph.D., reported at the San Antonio Breast Cancer Symposium.

"This is the first time in cancer we've found a biomarker that predicts response to preventive treatment. ... The point is, if your preventive intervention doesn't work, there's no point in pressing on for 5 years," explained Dr. Cuzick, chairman of the IBIS-I steering committee and head of the Cancer Research UK Centre for Epidemiology, Mathematics, and Statistics, London.

Scientific program cochair Dr. Powel H. Brown, who was not involved in IBIS-I, said the discovery that a reduction in breast density predicts benefit for preventive tamoxifen is "a major finding" that has the potential to be practice changing.

Many healthy women at high risk for breast cancer are reluctant to take tamoxifen because of concerns about toxicity. The new IBIS-I findings have the potential to increase adoption of tamoxifen therapy in eligible women because after just 12-18 months they'll have a very good indication of whether it's working for them. If their mammograms do not show a reduction in density, their physicians can take them off the drug so they can avoid its toxicities. If the breast density has decreased by at least 10%, however, they can be reassured that tamoxifen is working for them and is worth continuing because the risk:benefit ratio is quite favorable, said Dr. Brown, professor of medicine at Baylor College of Medicine, Houston.

IBIS-I randomized 7,154 women at high risk for breast cancer to 5 years of tamoxifen or placebo. At the latest follow-up, the tamoxifen group had a significant 27% decrease in breast cancer risk (J. Natl. Cancer Inst. 2007;99:272-82).

The new mammographic density analysis included 126 IBIS-I participants who developed breast cancer after their 12- to 18-month mammogram and 942 controls who remained cancer free during the first 5 years of the study. At baseline, 47% of the women had at least 50% of their breasts obscured by density.