Breast density signals tamoxifen’s effectiveness

Tissue density decline while on the drug predicts a better outlook for women at a heightened risk of breast cancer

SAN ANTONIO – Women with an elevated risk of developing breast cancer have the option of taking tamoxifen, a drug that has been shown to have cancer-preventive effects in these women. But the prevention isn’t complete, and like most drugs, tamoxifen carries a risk of side effects.
New findings from a large trial indicate that breast density measurements obtained from routine mammograms can reveal within a year or so whether taking tamoxifen as a preventive is worthwhile for a woman. Jack Cuzick of the Wolfson Institute of Preventive Medicine in London presented the findings December 12 in Texas at the San Antonio Breast Cancer Symposium.
Starting in the 1990s, Cuzick and his team enrolled more than 7,000 healthy women in the cancer prevention trial. The volunteers spanned a wide range of ages and had a moderately elevated risk of developing breast cancer — they had a sister or mother who developed breast cancer before age 50 or two close relatives who had developed it at any age.

Half the participants were randomly assigned to get tamoxifen and the others received a placebo. All the women underwent a mammogram at the start of the trial to establish breast density and got a repeat exam 12 to 18 months later.
Previous reports showed that over the course of the eight-year trial, women getting the antiestrogen drug tamoxifen were less likely to develop breast cancer than those on the placebo.
In the new report, the researchers investigated the effect of breast density changes by looking at the mammogram data from a sampling that included 504 of the women getting tamoxifen. In this subset, 48 had developed breast cancer despite being on the drug. The data show that women who experienced a reduction in breast density of 10 percent or more during the first 12 to 18 months on the drug were half as likely to develop breast cancer as were women getting a placebo. But women on tamoxifen whose breast tissues maintained their density despite the drug had a cancer risk about equal to those getting a placebo.
In general, women with dense breasts are four to five times as likely to develop breast cancer as are those without such dense tissue, says Cuzick. Previous work shows that tamoxifen reduces breast density, but precisely how the drug does so is not clear, he says.
A mammogram readily reveals if a woman has dense breasts, Cuzick says. And discerning changes in breast density between visits isn’t difficult for the average radiologist, he says.
But doctors read mammograms primarily to look for aberrant growths. “Doctors should be assessing mammogram density,” says Powel Brown, a medical oncologist at the Baylor College of Medicine in Houston. “In the future, I think it may well be good for helping us to decide who should be on tamoxifen.”
Women at high risk of cancer are those with a mutation in the BRCA1 or BRCA2 genes, or those who have had precancerous growth detected in their breasts. These women often get tamoxifen as a preventive, Brown says.

Women are judged to be at moderately elevated risk if they have a family history of breast cancer, have taken hormone replacement therapy or have never been pregnant, he says. These women face a more difficult choice. They can start taking tamoxifen, but the drug increases the risk of blood clot formation and — in postmenopausal women — increases the risk of uterine cancer. As a result, many women don’t take the drug, he says.
The new finding suggests that these women might soon have the more appealing option of trying tamoxifen for a year, having their breast density assessed, and then continuing if the drug succeeded in bringing down the density score, Brown says.
Tamoxifen is approved as a breast cancer preventive treatment in the United States but not in Europe.

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