A new target in breast cancer
Study aims to solve puzzle of ER-negative breast tumors
Myles Brown, MD, has organized a team of researchers to probe the unkinown of ER-negative breast cancer.
In the spring of 1998, officials notified some 13,000 volunteers in a nationwide breast cancer study that they were shutting it down 14 months ahead of schedule. The reason: it was already clear that tamoxifen, the estrogen-blocking drug being studied, could cut breast cancer incidence by half in these high-risk women.
The Breast Cancer Prevention Trial had enrolled healthy women with above-average risk of developing breast cancer. After four years, those who had taken daily tamoxifen were 50 percent less likely to develop invasive breast cancers than the women who took a placebo. With more than 200,000 cases of breast cancer diagnosed annually and 40,000 deaths in the United States, the trial outcome was great news, a milestone in cancer prevention.
Yet the triumph of tamoxifen was less than complete — and remains so.
While the drug can sharply reduce the risk of breast cancers whose growth depends on estrogen, it has no effect on cancers that aren't sensitive to the hormone. These "estrogen-receptornegative" or "ER-negative" cancers account for about one-third of breast cancers, or some 65,000 a year in the United States. Drugs like tamoxifen work by blocking estrogen's ability to trigger abnormal cell growth and are used to treat breast cancers as well as prevent them. Newer drugs called aromatase inhibitors, which may prove even more effective, directly block the production of estrogen. But if the cancers aren't ER-positive, none of these drugs is effective.
ER-negative breast cancer cells — unlike those in ER-positive tumors — lack structures called estrogen receptors on their surfaces. Estrogen molecules, therefore, have no port of entry to the cell. Something other than estrogen must be driving the growth and spread of these cancer cells, but scientists haven't discovered what it is. If they could identify the factor (or factors) at the root of ER-negative cancers, scientists might devise designer drugs that could home in on them. But there's been little research focused on ER-negative cancer.
"It's an untouched area," says Worta McCaskill-Stevens, MD, of the Division of Cancer Prevention of the National Cancer Institute (NCI). "The news about amoxifen is exciting, but we need to find a drug that works for estrogen-receptornegative tumors."
Myles Brown, MD, chief of the Division of Molecular and Cellular Oncology at Dana-Farber, agrees. Uncovering the causes of ER-negative breast cancer and finding better therapies "is one of the biggest unmet needs in breast cancer research," he says. Now, Dr. Brown and about 20 collaborators from Dana-Farber/Harvard Cancer Center (DF/HCC) and two other institutions have launched a major effort to go after the source of the puzzling and stubborn cancer.
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