BY KAREN SANDRICK

The state of the art of breast cancer imaging is in flux. Ultrasound and MRI have achieved a comfort level among radiologists for imaging certain indications. Ultrasound is used for distinguishing cysts from solid masses, guiding biopsy localization, and staging the breast and lymph node basins. MRI is called on to determine the extent of cancer and the presence of residual disease, document response to neoadjuvant chemotherapy, and spot recurrences.

These technologies are also carving out additional roles: ultrasound as a secondary screening examination in women with dense breasts and MRI for screening women at high risk for breast cancer. Their use, however, depends on local resources, experience, and patterns of practice, and it is not as widespread as it could be for one simple reason: lack of expertise.

FIGURE 1. Although breast MRI has extended into private imaging practice, most breast centers do not have the capability of MR-guided biopsy or localization. Women often must be worked up again at centers with expertise in breast MR needle localization. (Provided by E. Morris)

Breast sonography is invaluable for evaluating fibrocystic changes, identifying masses hidden on mammography, and further assessing palpable or mammographically detected masses when initial screening cannot provide a definitive diagnosis. Although mammography traditionally has been the method used for staging breast cancer, ultrasound offers additional information about axillary, infraclavicular, supraclavicular, and internal mammary lymph nodes, according to Dr. Gary Whitman, an associate professor of radiology at M.D. Anderson Cancer Center in Houston.

Two studies from Europe and Asia suggest that sonography helps in the identification of invasive lobular carcinoma and intraductal spread of breast cancer. In one, sonographic signs of malignancy such as irregular heterogenic, hypoechoic masses and posterior shadowing were found in 97 of 102 patients with invasive locular carcinoma in a retrospective analysis from the Centre Antoine-Lacassagne in Nice, France. In the other, sonography had a sensitivity of 89%, specificity of 76%, and accuracy of 85% in the detection of intraductal invasion in 46 breast cancer patients at Nagoya University School of Medicine in Japan.

Because of the high false-negative rate for mammography in women with dense breasts, ultrasound should be done routinely as a secondary screen for many postmenopausal women as well as for young women, said Dr. Thomas Kolb, an assistant clinical professor of radiology at Columbia University. About 40% of women in the general breast cancer screening population have dense breasts. This total includes 66% of premenopausal women, 40% of postmenopausal women on hormone therapy, and 25% of postmenopausal women who forgo estrogen replacement.

Kolb will soon publish results of his study of 150 women with mammographically dense breasts, in which mammography had a 22% miss rate. Bilateral whole breast ultrasound found 16 cancers over and above the 199 shown on mammography.

"With a screening ultrasound, we found that an additional 42% of women had cancers that were not palpable and invasive, which translates to an 80% increase in the number of cancers detected," he said.

Kolb envisions a screening procedure that combines digital mammography with digitally acquired ultrasound to overcome the ultrasound user's constant concern?operator dependence.

"During the same compression of the breast, you could acquire digital mammography, then run the transducer across the compression plate and get ultrasound data at the same time," he said. "You could look at the mammogram on a workstation, and if the breast is fatty, you won't even have to review the ultrasound data because the mammogram won't miss anything in a fatty breast. But if you find a questionable area on a mammogram in a dense breast, you can plunk down the x, y, z coordinates on the sonogram and decide whether it's a mass or a cyst."

Until combined digital mammography and sonography come to pass?or radiologists stop hemming and hawing about the operator dependence issue and improve their skills?sonography will serve primarily as a breast disease problem-solver and interventional guide, Kolb said.

Sonography will continue to occupy a narrow niche because it requires high-quality equipment, facilities for ultrasound-guided biopsy, and considerable operator skill and experience, Whitman said. At the same time, sonography commands low reimbursement, said Dr. Steven Harms, a professor of radiology at the University of Arkansas.

MRI TECHNOLOGY VS TRAINING

Breast MRI has generated a substantial amount of interest in the last few years because of its relatively high reimbursement, which may offset low-paying breast imaging services like mammography, Harms said.

MRI is no longer limited by hardware, said Dr. Elizabeth Morris, an assistant radiologist at Memorial Sloan-Kettering Cancer Center in New York City. There are breast coils and MR-guided titanium biopsy devices. A dedicated breast MR scanner from Aurora Imaging Technology of North Andover, MA, provides in one package all the tools necessary for generating high-quality, reliable breast images in a format that can be easily interpreted by other radiologists, said Harms, an Aurora consultant.

Breast MRI nevertheless is not being used much, said Dr. Gillian Newstead, director of breast imaging at New York University. A survey she conducted for the Society of Breast Imaging found that only about 200 of 650 breast centers were performing breast MRI.

A lexicon of terms developed by the International Working Group on Breast MRI, headed by Dr. Debra Ikeda, an associate professor of radiology at Stanford University, standardizes MRI interpretations. Yet no consistent formula exists for radiologists to follow

to produce consistently high-quality breast images, Harms said. Radiologists and technologists have not mastered the technique because of an overall lack of specific training.

"The radiologists who do standard MR interpretation are not accustomed to managing breast patients. They are used to neurological and musculoskeletal problems, and the breast is a completely different thing," Harms said.

Morris described the other side of the coin, acknowledging that most radiologists skilled in breast imaging are mammographers who have never been in a magnet. They think of MR as complicated, requiring many different sequences, she said.

"There's a lot of hand-holding before people develop confidence in their ability to interpret the studies," Morris said.

Some breast imaging centers in tertiary-care facilities as well as in private practices are nonetheless starting to routinely apply breast MRI to women with known malignancies. At Memorial Sloan-Kettering, breast MRI is the gold standard for assessing the extent of breast cancer before surgery. The technique defines the size of breast tumors and locates any additional foci in the breast, effectively mapping out the entire tumor burden so the surgeon can tailor the operative approach to conserving the breast, Morris said.

At breast centers such as Memorial Sloan-Kettering and NYU, MR is used for patients with metastatic disease in the axilla when mammography and ultrasound cannot find primary breast tumors. MRI also evaluates the response to neoadjuvant therapy in patients with locally advanced, stage III breast cancer.

"Many of these patients are young and have rapidly growing tumors. MRI is the most sensitive way of looking at the volumetric response of the tumor to the chemotherapy," Newstead said.

FIGURE 2. Multifocal carcinoma in a 57-year-old woman. A: Irregular mass is seen in the outer right breast on craniocaudal mammogram. B: Sonography showed a hypoechoic right breast mass with irregular, lobulated margins at 7 o¹clock. This mass corresponded to the mammographic findings. Core biopsy revealed carcinoma. C: In 7-8 o¹clock position of the right breast, hypoechoic satellite lesion closest to the primary tumor was 2.5 cm from the main tumor mass. D: Ultrasound-guided core biopsy was performed on a satellite lesion noted 4 cm from the primary tumor. Pathology revealed carcinoma. Right mastectomy was performed, and multifocal lobular carcinoma was identified on histopathologic examination. (Provided by G. Whitman)

Another major indication for breast MRI is to search for evidence of residual disease after lumpectomy when tumor margins are grossly positive. Within the first few weeks following breast-conserving surgery, radiologists will use MRI to determine how much and where cancer remains along the operative cavity, so surgeons can decide whether to reoperate and extend the lumpectomy site or resort to mastectomy. Also at the lumpectomy site, MRI differentiates between scar tissue and disease recurrences, Newstead said.

HIGH-RISK SCREENING

Screening women at high risk for breast cancer is a new area for MRI, but Harms is confident that data will support expanded use.

"Screening high-risk women is not an indication for MRI, but if and when it is proved that the technique is effective and insurers routinely pay for it, we won't have enough MRI machines to accommodate the volume. This will be a major clinical role for MRI," he said.

Although study samples are small, initial reports from clinical trials of MRI in high-risk women appear to bear him out. MRI identified all six invasive cancers that occurred in 196 women who were carriers of BRCA1 and BRCA2 mutations or had strong family histories of breast or ovarian cancer in a study by the Centre for Research in Women's Health at Sunnybrook and Women's College Health Sciences Centre in Toronto. All six cancers were 1 cm or less in diameter and had not spread to the lymph nodes. In the study, mammography and physical examination each detected two of the cancers, and ultrasound found three.

In a study from Erasmus University in Rotterdam, the Netherlands, MRI found malignancies in three of 109 patients who had a greater than 25% risk of breast cancer. The malignancies, confirmed by histology to be T1bNO and T1cNO, were hidden to mammography and not palpable. MRI produced false-positive findings in six women but no false-negative results.

On the basis of a preliminary study, Memorial Sloan-Kettering is offering MRI to patients who have BRCA1 or BRCA2 genetic mutations or a history of lobular carcinoma in situ or atypia. The study, which collected data on about 150 high-risk patients, found three cancers with MRI that were not detected by mammography. All the cancers were early-stage T1 disease, and the women were node negative.

As radiologists in the community become more accustomed to breast MRI, the technique is bound to assume a position at the leading edge of cancer imaging. In as little as five years, breast MRI will be a regular part of the workup of patients with breast problems, according to Newstead.

But MRI will be only one of many imaging options for assessing the breast. Radiologists will need to offer the full gamut of breast imaging techniques and tailor examinations to the lesion, the breast parenchyma, and the specifics of the clinical situation, Whitman said.

"A lesion that has calcifications probably is going to be imaged best by mammography," he said. "For obscured masses in a dense breast, mammography has limitations, and sonography may be of value. There is a great deal of effort to identify women at high risk for breast cancer, and there will be strong emphasis to develop effective screening for these women. One of the exciting areas is the use of MRI to help assess response to treatment by allowing us to get a feel for the size of a lesion as well as the microenvironment or vascularity of the lesion."