USC Health Now

Radiologists are improving current breast cancer imaging techniques to better detect tumors and discern masses.

USC Health Magazine
Fall 2005
by Alicia Di Rado

The message has been spread far and wide: Breast cancer is most treatable when it is caught early, so women should be vigilant and get routine testing to find tumors when they are still tiny and have not had the chance to spread.

Unfortunately, some women find that despite their best efforts—and the persistence of their physicians—tumors still slip by, going undetected until their size makes them impossible to hide.

So Keck School of Medicine radiologists, knowing that the lives of mothers, daughters and sisters are at stake, are fast-forwarding imaging technology to uncloak more of these tumors.

The stakes are high: Breast cancer remains the most common cancer other than skin cancer among women. And despite advances, the disease continues to take its toll. Breast cancer trails only lung cancer as a leading cause of cancer death among American women.

Radiologists at the Keck School and USC/Norris Comprehensive Cancer Center are conducting a flurry of clinical trials to look for answers to some of the most vexing challenges to women’s breast health: detecting tumors that are hard to discover in dense breast tissue, better discerning the difference between harmless masses and malignant lesions, and making breast cancer imaging more accessible and affordable.

“There’s a lot of work going on to push technology forward in women’s imaging,” said Yuri Parisky, M.D., associate professor of clinical radiology and director of new technologies at the Harold E. and Henrietta C. Lee Breast Center at USC/Norris.

Parisky and assistant professor of clinical radiology Linda Hovanessian-Larsen, M.D., are forging ahead on projects that snip away at breast cancer’s deadly shroud.

Dense detection

Hovanessian-Larsen, for one, is looking for answers to one of radiologists’ most difficult conundrums: how to better find and assess breast cancer early in young women, whose dense breast tissue can often hide suspicious lesions. Older women using hormone replacement therapy also may have dense breasts.

Dense tissue complicates mammography. While fat appears black on a mammogram, cancer appears as a white mass, Hovanessian-Larsen explains. Unfortunately, normal, dense glandular tissue also appears white on a scan—sometimes obscuring cancerous tissue.

“Mammography in fatty breast tissue provides 98 percent accuracy,” says Hovanessian-Larsen, director of the women’s imaging division in the Department of Radiology. “But in dense breasts, accuracy goes down to 40 to 60 percent.”

Strictly considering the numbers, accurate imaging would seem to be most important in women who have already gone through menopause. More than three quarters of women with breast cancer are age 50 or older at diagnosis—a proportion that dwarfs the 0.3 percent of women with breast cancer who fall between ages 20 and 29 at diagnosis.

But the cancers can certainly happen in young women, and their numbers tend to increase throughout their 30s and 40s. Women with a strong family history of the disease, too, may be more likely to develop a tumor at a fairly early age. Moreover, the younger a woman is at diagnosis, the more aggressive her tumor is likely to be—making it critical that it be caught early.

Hovanessian-Larsen believes ultrasound techniques can help women at high risk for breast cancer, in particular. Ultrasound uses sound waves to form a picture, and some studies suggest it can find early breast cancers in dense breast tissue. It is relatively inexpensive, widely available and well tolerated by patients. That is why she is involved in an extensive American College of Radiology Imaging Network (ACRIN) trial that evaluates whether ultrasound should be used together with mammography as a screening method in women with dense breast tissue who are at high risk for breast cancer.

Radiologists already use ultrasound as part of diagnostic breast imaging. Imaging is considered diagnostic—rather than a general screening tool—when physicians use it to assess breast tissue after a woman or her examining doctor has found a mass, dimpled skin on the breast, unusual expressed fluid or other suspicious symptoms.

So far, though, physicians have had no reason to use it as a part of routine screening, as they do with mammography. It cannot consistently or reliably show some early signs of breast cancer as well as mammography can among most women who need regular breast cancer screenings. But for women with dense breast tissue at high risk for breast cancer, ultrasound might turn out to be a valuable addition to mammography in the screening process. Already, research efforts have shown that ultrasound doubles the detection rate of cancer in women with dense breasts.

USC and about 21 other North American sites are recruiting 2,800 women for the ACRIN study, which is sponsored by the National Cancer Institute and the Avon Foundation. All participants receive a mammogram and ultrasound each year for three years. Two radiologists look at each scan independently and then discuss the results.

“We look for an irregular shape, darkness of the lesion and shadowing on ultrasound,” explains Hovanessian-Larsen, who leads USC’s ACRIN trial site, which includes USC/Norris and LAC+USC Medical Center. “Through this study, we want to better characterize the differences between solid masses: between benign ones and malignant ones.”

The study will cover the ultrasound cost, but women must have insurance coverage for the mammography. Eligible women include those with a personal history of breast cancer or a strong family history of breast cancer, or those who have had a breast biopsy showing pre-cancerous cells.

High contrast

In a separate, pilot study exclusive to USC/Norris, Parisky wants to see if existing technology can make mammography even more effective.

In this study, USC/Norris radiologists are using the Selenia unit, a digital mammography system produced by Hologic Inc., which is supporting the study.

Like traditional mammography, Selenia uses X-rays to create an image of women’s breast tissue; but instead of recording images on film, digital mammography records images electronically. That means radiologists can darken or lighten the images, manipulate them and share them electronically with other health experts.

Parisky and fellow radiologists are testing whether injecting a contrast agent into women undergoing digital mammography can provide more information about a woman’s cancer than mammography alone.

“We want to blend those two elements—contrast and mammography—to see if they could give us information about whether a lesion is benign or malignant, as well as extent of disease,” Parisky says.

Radiologists routinely use contrast agents as a way to highlight cancer’s appearance on magnetic resonance imaging, or MRI, scans. “We know breast tumors have a greater blood supply than normal tissue, and the contrast picks that up,” Parisky says.

Bringing contrast to digital mammography could offer benefits, he notes. Clinics have much greater access to mammography than MRI, and mammography is more affordable than MRI.

Also, if radiologists can use digital mammography with contrast to more reliably tell if a lesion is malignant or benign, patients may be saved the stress and costs of having a biopsy, only to find the mass was harmless.

USC/Norris radiologists will recruit 20 women to participate. They will select patients known to have a suspicious lesion requiring biopsy. The team will perform digital mammography with contrast and try to identify the lesion and its characteristics from the scan; the team will then compare those findings with pathology results from the patient’s subsequent biopsy. Some patients also will undergo MRI.

Bright light

Radiologists also are investigating other breast imaging techniques.

One is tomosynthesis, which uses X-rays, like mammography. However, in tomosynthesis, the imaging machine takes pictures of the breast from a series of different angles, resulting in a three-dimensional series of high-resolution slices through the breast. Mammography alone only shows one view of the breast tissue.

Through tomosynthesis, radiologists may be able to better see lesions or suspicious areas that would otherwise overlap each other on a traditional mammogram, Parisky says. Also, each image taken by tomosynthesis provides a fraction of the radiation dose used in today’s typical mammography scan. Other techniques do not use X-rays at all.

Pulin Sheth, M.D., Keck School assistant professor of clinical radiology and director of breast imaging at USC/Norris Lee Breast Center, leads a study using the DOBI Medical ComfortScan system, an experimental, non-invasive digital imaging system that uses high-intensity light to highlight any areas of a woman’s breast with vascular abnormalities.

One of cancer’s hallmarks is that a tumor must surround itself with tiny blood vessels that bring it nourishment; the ComfortScan system aims to pinpoint those telltale blood-vessel hotspots.

During the ComfortScan, a woman stands in front of a machine that features a panel of red light-emitting diodes and a silicone membrane. The membrane inflates around the breast and exerts gentle pressure while light shines through the breast tissue. A camera then measures variations in the intensity of light transmitted through the breast.

If the light encounters an area of breast tissue with an unusual abundance of capillaries, it is absorbed into tissue differently because of the higher concentration of hemoglobin (found in the blood) in the area. That results in variations in light intensity.

When used together with mammography, such imaging systems may give physicians far more information about the health of a woman’s breast than ever before.

“This is an exciting time,” sums up Hovanessian-Larsen, who credits the expansion of radiologic research to Edward Grant, M.D., Keck School chair of radiology. “He is really supportive of all of us and our efforts to get research going in radiology.” ?

For more information about the Department of Radiology, or to learn more about any of The Doctors of USC, call 1-800-USC-CARE. For information about the breast imaging studies, call project manager Tina Kiss at (323) 865-3228.

CHECK YOU OUT

Women can use three routine methods to watch for breast masses: mammography, self-exam, and a breast exam by a doctor.

Various groups, such as the Susan G. Komen Breast Cancer Foundation, the American Cancer Society (ACS) and National Cancer Institute (NCI) differ slightly in their recommendations on how often to use these screening methods.

Mammography is considered the gold standard for screening. Researchers have shown that this imaging technology can cut the number of breast cancer deaths by 48 percent for women between ages 40 and 74. Accordingly, women should get a mammogram every year beginning at age 40, according to the Komen Foundation and the ACS. The NCI recommends a mammogram every one to two years beginning at age 40.

Self-examination entails a woman feeling for unusual lumps in her breast. The ACS recommends each woman discuss with her physician whether to perform breast self-examination regularly, while the Komen Foundation recommends that monthly self-exams begin by age 20. The NCI makes no self-exam recommendations.

As for clinical breast exams—focused, physical examinations conducted by a health-care provider—both the Komen Foundation and ACS recommend they be done at least every three years between ages 20 and 39, and annually beginning at age 40. The NCI, again, makes no recommendation.

Women with a significant family history of breast cancer or those who are otherwise considered at high risk for the disease may need to begin screenings earlier or have additional routine testing, depending on the recommendations of their physician