Density Danger
Women with dense breasts have a greater likelihood of cancer
When Pam Schmid got a baseline mammogram in her 30s, the radiologist remarked that she had dense breasts. And that was that. "I remember thinking, 'I don't know what that means,'" says the Raleigh, N.C., wellness coach, now 49. Eventually, it meant a belated discovery of cancer. In 2003, Schmid felt a lump in her breast, and it turned out she had several tumors.
After a grueling series of treatments-mastectomy, chemotherapy, radiation, and hormonal therapy-Schmid is now in remission. But she wonders if understanding the implications of breast density at that first appointment might have led to an earlier diagnosis. Doctors are only now widely realizing that a high proportion of dense, nonfatty tissue in a woman's breasts trails only her age and rare mutations in the BRCA genes at upping the odds of developing cancer. "Beyond a doubt, it's an important risk factor," says Norman Boyd, an epidemiologist at the Ontario Cancer Institute in Toronto. In a study published last month in the New England Journal of Medicine, Boyd and his colleagues reported that when at least 75 percent of a woman's breast tissue is dense, she has about five times as high a chance of developing breast cancer as someone with very little dense tissue. That's a scary stat, given that about a quarter of women are believed to hit at least the 50 percent mark.
So there's a new sense of urgency about uncovering explanations. Until now, many physicians have believed dense tissue to be dangerous only because it can cloak tumors on a mammogram. How, exactly, might it lead to tumors? Scientists don't know, though they have some ideas. Dense tissue (which shows up as the light areas on a mammogram) contains different types of connective tissue and epithelial cells, which support and line the body's organs. Epithelial cells throughout the body give rise to most tumors; in the case of dense breasts, researchers suspect that some process involving connective tissue helps nascent tumors take root and grow. (Collagen, a type of connective tissue found in tumors, is found in greater proportion in dense breasts.)
Hormones found in fatty tissue could play a role, too, says James Cerhan, an epidemiologist at the Mayo Clinic College of Medicine. It may in fact be a dialogue between dense and fatty tissues that increases the risk of cancer. Locating the genes responsible for breast density, researchers hope, will provide clues about the mechanism that produces cancer-and a better understanding of why some women have dense breasts and others don't.
Next steps. It's way too soon to say whether altering a woman's breast density might lower her risk of cancer, but researchers are exploring ways to do just that. Since density changes in response to levels of sex hormones-decreasing after a woman gives birth and as she ages and reaches menopause-it's possible that drugs might make a difference, too. It's already clear, for example, that hormone therapy that includes both estrogen and progesterone increases density by stimulating the growth of the epithelium and connective tissues. Tamoxifen reduces density by shrinking those tissues. Meanwhile, a study released last week led by Melinda Irwin, a researcher at the Yale School of Public Health, found that exercise reduced density in obese postmenopausal breast cancer survivors. There's also some evidence associating greater density with consumption of fat and alcohol, but those links have yet to be established.
While science searches for answers, women should quiz radiologists about their own breast density now. "I'm of the school that the more you know, the more your power is," says Mary Daly, head of the Margaret Dyson Family Risk Assessment program at Fox Chase Cancer Center in Philadelphia. There's no need to panic. While their risk is higher, most women with dense breasts won't get cancer: Boyd says a 50-year-old woman with density in more than half her breast still has only about a 5 percent chance of getting breast cancer in the next decade, compared with about 2.5 percent for the average 50-year-old woman. But a few precautions may be in order. Talking to a doctor about the potential danger of using combined hormone therapy may be wise, for example. The jury's still out on other interventions.
And there's good reason to be extra diligent about being screened, possibly by one of the newer technologies (box). A study published in 2005 showed that digital mammograms are more effective than traditional ones using X-ray film at detecting cancer in women with dense breasts. Studies of ultrasound's power have also been promising; researchers funded by the National Cancer Institute and the Avon Foundation will issue a preliminary report this autumn on whether there's evidence that ultrasound screening in these women can reliably pick up tumors not detected by a mammogram. If so, the American Cancer Society will review whether its screening recommendations should add ultrasound to mammography for women with dense breasts, says Robert Smith, the organization's director of screening.
In the meantime, a woman with dense breasts can ask her doctor whether it's worthwhile to seek out either technology. That may be tricky and costly-digital mammography is available in only about 15 percent of imaging facilities, for example, and insurance might not cover the full cost. About 35 percent of facilities can do ultrasound.
In any case, a mammogram is the first line of defense, says Wendie Berg, a radiologist and breast imaging consultant in Lutherville, Md., and head of the ultrasound trial. "If it's convenient, it's probably a good idea to have it done digitally, but it's less important than to have a regular one at a good facility," she says. Regular clinical breast exams are a must, too.
Pam Schmid, whose tumor didn't show up on a mammogram, is a big proponent of the low-tech self-examination. She felt a lump during her regular check, agreed to a wait-and-see period of six months, then insisted on an ultrasound. One tumor showed up, and a subsequent MRI revealed four. Schmid urges women to ask their radiologists to explain mammogram results, find out the density percentage of their breasts, consider further imaging, and trust their intuition.
At this point, there are clearly more questions than answers about density and cancer. But because of the number of women affected, the implications of finding answers are huge, says density researcher Jack Cuzick, head of the department of epidemiology, mathematics, and statistics at the Wolfson Institute of Preventive Medicine in London. Assuming that it is possible to lower risk by lowering density, he says, getting women with 50 percent density down to 15 percent "could eliminate a third of breast cancer."
A Clearer Picture?
Regular film mammograms (right) remain the gold standard. But other, more sensitive technologies are in use or under study for certain groups of women, including those who have dense breasts. They may be expensive and hard to find, but if you're at elevated risk of breast cancer, talk to your doctor about:
Digital mammography. Computer-generated testing works about as well as regular mammograms in most women, but it is more effective at spotting trouble in younger women and those with dense breasts.
Ultrasound. At the moment, ultrasound-which uses sound waves to create an image of the breast-is prescribed as a follow-up to evaluate lumps and other abnormalities.
Magnetic resonance imaging (MRI). This supersensitive test produces a lot of false positives and is more onerous than mammography. It's not used as a general screening test but rather as a tool to assess known cancers or to screen women at very high risk of breast cancer.
Digital tomosynthesis. This new technology creates a 3-D picture of the breast using multiple X-rays. It may find cancers not seen on a mammogram. For now, tomosynthesis is available only for research purposes. But stay tuned.
This story appears in the February 12, 2007 print edition of U.S. News & World Report.