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http://www.nytimes.com/2002/09/19/health/19BREA.html?tntemail0

Dense Breasts May Need Sonograms to Detect Cancer

By SANDEEP JAUHAR

reast density, a known risk factor for breast cancer, may be inherited, and there are indications that women with dense breasts may need to be screened with ultrasound, two studies said today.

Researchers in Canada, Australia and New Zealand studying identical and fraternal twins found that variations in breast density were strongly influenced by genetic factors, a study in today's New England Journal of Medicine found.

The other study, of 11,130 women at a Manhattan radiology clinic, found that ultrasound examinations, or sonograms, could detect a significant number of cancers that were missed by mammography in women with dense breasts. The authors, writing in the journal Radiology, argue that screening by ultrasound may be useful in this population. But the study is not considered definitive because the patients were not selected at random and it was performed by just one researcher.

Dr. Stephen Feig, director of breast imaging at Mount Sinai Hospital in Manhattan, said that the ultrasound findings were impressive, and that "anything we can do to increase breast cancer detection we should do if it is feasible."

But Dr. Feig said he was concerned about the limited nature of the study and the time and expense of screening a wider population with sonograms, which cost about $150, roughly the same as mammograms.

"We need to learn more before screening breast ultrasound becomes standard of care," Dr. Feig said, adding that a multicenter trial of such screening was being organized.

It is well known that mammograms, even at their best, miss a lot of cancer, up to 25 percent in women under 50. Young women tend to have dense breasts, which appear white on mammography, making it harder to differentiate small tumors.

Women with very dense breasts, composed primarily of fibrous tissue and milk-producing glands, have four times the risk of developing breast cancer as women of the same age with fatty breasts. Experts suspect that dense tissue means more cells that could potentially become cancerous, but no one is sure.

Research has shown that breast density appears to decrease with age and the number of children a woman bears, and increase with hormone replacement therapy. Because breast size and texture are not reliable predictors of breast density, many women are unaware that they have dense breasts. Mammography is the only accurate test.

In the New England Journal study published today, researchers performed mammograms on 571 identical twins and 380 fraternal twins ages 40 to 70 in Australia, Canada and the United States. They looked for correlations in the degree of breast density within pairs of twins.

Identical twins have identical genes, so that any differences in breast density between them would most likely be because of environmental factors or measurement error. Fraternal twins, on the other hand, on average share only half their genes. The researchers found a much stronger correlation in breast density between identical twins than fraternal twins, suggesting that the contribution of genetic factors to breast density is 60 to 75 percent.

An unsettled question is how women with dense breasts should be screened. Ultrasound has been widely used to evaluate suspicious abnormalities on a mammogram, but whether it should be used as a screening tool for the wider population has been a matter of debate. Several studies in the 1980's showed little benefit of screening breast ultrasounds, and in 1994 the American College of Radiology said that sonograms should not be used to screen for breast cancer.

The latest research, by Dr. Thomas Kolb, a Manhattan radiologist and the lead author of the study, confirmed that mammography misses a substantial number of cancers in dense breasts. In the study, 11,130 women without any signs or symptoms of breast cancer received screening mammograms and a breast examination from January 1995 to September 2000. Seventeen percent of the women had a history of breast cancer, and 78 percent had a normal breast examination within one month of the study. Roughly half the women were assessed to have dense breasts and received an ultrasound examination.

The study detected 246 cancers, of which 83 percent were invasive; the rest were in situ cancers that are often surgically treatable. Consistent with previous results, mammography detected 98 percent of cancers in women with fatty breasts but only 48 percent in women with the densest breasts, assuming that the screening tests found all cancers.

Ultrasound detected 33 additional cancers in the roughly 5,000 women with dense breasts who had normal mammograms and breast exams. Seventy percent of these cancers were smaller than one centimeter and 89 percent did not involve lymph nodes, suggesting that they were at an early stage.

"A sensitivity of 48 percent for mammography in women with the densest breasts is unacceptable," Dr. Kolb said in a phone interview. "Screening ultrasound will find an enormous amount of cancer that would otherwise go undetected."

To detect the 33 cancers, 320 biopsies had to be done, resulting in a positive biopsy rate of just 9 percent.

"I think the trade-off happens to be very reasonable," Dr. Kolb said. "Speak to as many women as I do, and you will find near unanimity for having a screening ultrasound because women realize that a low positive biopsy rate is a minimal consequence to the potential benefit."

But even if ultrasound detects more cancers, experts said, there is no evidence it will save lives. "Are these cancers that would have gone on to cause trouble for these women?" Dr. Steven Goodman, professor of biostatistics at Johns Hopkins School of Medicine, asked. "It's the $64 million question." Without data on outcomes like disability or death, he said, this study could not provide an answer.

"It's a given that the more tests you do, the more cancers you're going to pick up," Dr. Barry Kramer, a cancer specialist and associate director for disease prevention at the National Institutes of Health, said. "There's an unwritten assumption that finding any cancer is good, but there isn't enough evidence to guide that particular judgment."

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