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Beyond Mammography (video)
March 08, 2001

Gail Bado will never forget the day she learned she had breast cancer. "It was shocking," she says, "like an out of body experience. My heart was heavy and I was very upset."

A routine mammogram had uncovered a tiny tumor. Her doctor said it was not cancer, but Gail sought a second opinion. "I was lucky enough to have my sensors raised enough to say I think we might want to go ahead and biopsy it," says Dr. Rebecca Zuurbier, a radiologist at Georgetown University Medical Center. "So it was a very subtle mammographic finding but ultimately a very important one."

For the 180,000 women diagnosed with breast cancer each year, mammograms, although imperfect, are still the most reliable method available to detect the disease. But a report released today by the National Institute of Medicine says there are promising new technologies on the horizon.

A blurry image

Mammograms can not only be interpreted differently, but they can also simply miss as many as 15 percent of breast cancers. That’s why the Institute of Medicine of the National Academy of Sciences backed a study called "Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer."

In a typical screening mammogram, two X-rays are taken of each breast. The radiologist examines the film on a light box, comparing the two breasts for areas of asymmetry and extra density. "It’s like our eyes become a bar code scanner," says Zuurbier.

Dr. Rebecca Zuurbier and mammogram
Dr. Rebecca Zuurbier of Georgetown University Medical Center studies a mammogram.
Usually it works. Routine mammography screening can reduce the number of deaths from breast cancer by 25 to 30 percent for women between the ages of 50 and 70 (the percentage is lower for women aged 40-49), according to the study. The study showed that mammography remains the best way to detect breast cancer early.

Yet analyzing a mammogram is not always cut and dried. "Mammograms are difficult to interpret in any patient who has a dense breast or a heterogeneous breast," says Zuurbier. "Some women’s breasts look like very complex abstract paintings," she explains. "For example, Jackson Pollock comes to mind when I interpret some of these paintings: lots of splotches and dots. So breast cancers have an easier time hiding in these very complex-pattern breasts." Cancer can also be hard to spot if a patient has had implants, she says.

A clearer picture

But there are several new screening technologies that could one day make it much easier to detect breast cancer. "We saw some fantastic technology," says Dr. Daniel Hayes, a committee member of the study who is also Clinical Director of the Breast Cancer Program at Georgetown University Medical Center. "Some Star Wars stuff—where you couldn’t help yourself from saying ’gee whiz.’ It was like going to the electronics store and pulling out all the new devices."

breast MRI
Breast MRI.
image: Dr. Donald B. Plewes, U of Toronto

Some of the techniques, such as breast MRI (magnetic resonance imaging), digital mammography, or techniques that analyze temperature, optical, electrical or elastic properties of the breast, are expected to provide better images.

In MRI, already widely used to diagnose disease in other parts of the body, an image is generated by measuring how tissue responds to a magnetic field. Although it needs to be refined to detect breast cancer (it can’t always distinguish malignancies from harmless abnormalities), the study found that it could be helpful for a patient whose mammogram isn’t clear.

Digital mammography, which still uses X-rays but generates a computer image, is another possibility. Right now, it improves contrast and the image can be manipulated much like you change the contrast on your television screen, but the fine detail resolution is not as good as a conventional mammogram, says Zuurbier. "I am not sure it’s going to be a great revolution in women’s health care, but I am betting that within ten years I will be looking at mammograms from a computer screen instead of a piece of film," she says.

A molecular view

Besides new imaging techniques, scientists are trying to identify breast cancer at the genetic level. Only 10 percent of breast cancer stems from inherited susceptibility (such as the BRCA1 and BRCA2), so scientists are looking at genetic changes that occur during a person’s lifetime.

Researchers at the National Cancer Institute (NCI) have developed a new approach that identifies protein markers that may be associated with the early development of the disease. "The proteins are made by the genes and they carry out all the function of the cell. They are sort of the unsung heroes," says Dr. Lance Liotta, chief of the pathology laboratory at the NCI. "You hear a lot about genes, but the proteins really do all the work," says Liotta. They do it by connecting to other proteins in circuits and sending signals which communicate with other parts of the cell and the rest of the body as well, he explains.

Infrared image of a breast
Infrared image of a breast.
image: NASA

Liotta says that if doctors can identify new markers for early stage disease, then they can effectively reduce the impact of cancer. "We know as scientists and as doctors that cancer begins as microscopic lesions in the tissue of the body," he explains. "And these microscopic lesions, too small to see with the naked eye, evolve over time and then become manifest as invasive and malignant tumors, which then spread into life-threatening metastases for the patient. Oftentimes we diagnose the cancer when it’s too late and the therapy doesn’t have the effect we hope it will have, so our goal has been to develop new technology to study the early stage cancer when it’s at that microscopic level."

To do that, Liotta and his team examine tissue from biopsies under a special microscope that they invented. They then separate the microscopic areas of early cancer from the normal tissue. "We use this invention called laser capture microdissection that allows us to use a laser beam like a tractor beam and pull out only the cells we want to study," Liotta says. By comparing normal cells to cancer cells and separating the proteins to come up with a protein fingerprint, they can look to see which ones are changing, thereby finding markers.

"We believe that it is a completely revolutionary new approach toward finding markers, finding new imaging agents, and also finding specific targets for drugs to prevent and treat cancer," says Liotta. "And since for the first time we are studying the proteins that are actually changing in the real human tissue, we are finding proteins that you can’t find by any other method. You can’t find it by culturing cells in a test tube, or by studying experimental animal models. We are looking at the actual evolution of the cancer in the real human tissue."

A realistic view

Blue Laser
LASER technology
image: Imaging Diagnostic Systems, Inc.

While Liotta envisions a future where breast cancer will be diagnosed via protein markers and treatment will be tailored to individual patients, the Institute of Medicine study showed that right now, mammography remains the gold standard in early detection. "There is a huge gulf between the gee-whiz technology and actually getting it to the point where we know that it has at least the same or hopefully a better impact than mammography does," says Hayes.

"There’s no test or set of tests that will replace screening mammography in the near future," says Zuurbier. Other experts share this opinion. "Right now, all the technologies that we have been looking at that are relataively new...are adjuncts to mammography," says Dr. Craig Henderson, vice chair of the study and and adjunct professor of medicine at the University of California, San Francisco. "None of them will replace mammography based on any information or any use that we have at the present time." The American Cancer Society recommends that women aged 40 and older have a screening mammogram every year.

Hayes says that while there is still some controversy, most experts accept that screening mammography does reduce the chances of a patient’s dying of breast cancer. Many patients would also agree. "A mammogram saved my life," says Gail Bado. "So I really have begun to believe that it should be routine for women to protect themselves."

Elsewhere on the web

American Cancer Society’s Breast Cancer Resource Center

Breast Cancer Risk Assessment Tool

Info on breast cancer from CancerNet (NCI)

Search for clinical trials

National Breast Cancer Coalition

Breast cancer info from OncoLink

by Jill Max

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