Beyond the Mammogram: Molecular Breast Imaging Emerges

While the digital mammogram is still considered the gold standard for breast screening, those who need additional imaging have new options. Enter nuclear breast imaging, the catch-all phrase for several modalities that use a radiopharmaceutical agent in scanning, including gamma imaging and positron emission mammography (PEM). Known as both molecular breast imaging (MBI) and breast-specific gamma imaging (BSGI), the gamma cameras are an adjunctive technology for suspicious lesions found during mammogram.

While the mammogram is still considered the gold standard for breast screening, those who need additional imaging have new options. Currently, MRI is the traditional next step for the about 30 percent of women with dense breasts, those with positive BRCA1/BRCA2 mutations, and women with suspicious lesions. The times, they are a-changing, though, with recent advances in breast imaging technology. Not all women can undergo an MRI, and it’s a more expensive and time-consuming study to read than newer modalities.

Enter nuclear breast imaging, the catch-all phrase for several modalities that use a radiopharmaceutical agent in scanning, including gamma imaging and positron emission mammography (PEM). Known as both molecular breast imaging (MBI) and breast-specific gamma imaging (BSGI), the gamma cameras are an adjunctive technology for suspicious lesions found during mammogram. Physicians are also using it in place of MRI for women who are unable to tolerate that study or have metallic implants.

Many use the terms MBI and BSGI interchangeably, however the machines use different technology. BSGI uses a sodium iodide scintillator technology developed by Dilon Technologies (the only company developing such a technology), and MBI uses cadmium-zinc-telluride digital detectors developed by the Mayo Clinic.

“We have been using breast-specific gamma imaging since 2007, primarily for high risk individuals with difficult mammograms and/or sonograms, dense breasts, and for the evaluation of asymmetric densities,” said Barbara Ward, MD, a partner in Weinstein Imaging Associates in Pittsburgh, Pa.

“One of the most helpful and important uses of this modality is for patients who present with a palpable abnormality with a negative mammogram and ultrasound,” she said. “If the subsequent BSGI is negative, the patient has been very reassured. On the other hand, we have picked up some cancers that were both mammographically and sonographically occult with BSGI.”

Gamma Imaging

The Dilon 6800 is the machine currently used by those performing BSGI studies. This technology detects Tc-99m sestamibi uptake, with a single-head gamma camera. It can typically detect lesions as small as 3 mm in diameter.

Researchers at the Mayo Clinic developed a dual-head gamma camera which also detects Tc-99m sestamibi uptake in suspicious breast lesions. Gamma Medica licensed the technology and recently introduced it commercially as the LumaGEM MBI System, which can reportedly detect lesions 1.6 mm in size, while using less radiation exposure. This is important because the major concern with any nuclear breast imaging system is that “it’s about 25 times the radiation dose of a mammogram,” according to Emily Crane, research director and co-author of KLAS Breast Imaging 2010: A More Complete Picture, an independent healthcare vendor performance report released in December.

The Gamma Medica product is so new that KLAS researchers were unable interview any sites using the technology on a non-research basis.

While MBI is not used as a primary screening tool, its use as an adjunctive modality has shown efficacy. A study from the Mayo Clinic, published in the January 2011 issue of Radiology, compared MBI to mammography in 936 at-risk women. The authors found that sensitivity for mammography alone was 27 percent, while MBI and mammography combined had a sensitivity of 91 percent. In that study, 11 cancer diagnoses were made. MBI alone detected seven of the tumors, while one was detected by mammography alone, one by both techniques combined, and one by neither.

Screening Women with Dense Breasts

The gamma cameras are a popular technology to use for women with dense breasts. It’s estimated that two-thirds of women in their 40s have dense breasts, decreasing to around one-third of women 50 and older. Due to the nature of X-ray technology, it can be difficult to interpret mammograms on dense breast tissue because the tissue and tumors both show up white.

“Sometimes [a mammogram] is nearly useless in really, really dense breasts,” said Seetaram Ravipati, MD, a radiologist at Grand Lake Health System in St. Marys, Ohio. He said that if the BSGI is negative in a young woman with dense breasts, he’s more comfortable using just a mammogram for the next few years. “Breast cancers don’t grow overnight - it takes two to five years,” he said, adding that he can rely on mammograms for their limited use, because he knows the BSGI was negative. He said that if the patient developed a breast cancer in the next few years, hopefully the mammogram would show a more obvious dense lesion.

BSGI versus MRI

Of course MRI is used for similar reasons, however not all patients can tolerate an MRI, or it could be contraindicated. Another concern with MRI is financial. MRI costs three times as much as gamma imaging studies. Facilities who provide BSGI screening report no problems with reimbursement from Medicare, Medicaid, or third party payers, and they use available nuclear medicine billing codes.

Ravipati said his facility started using the Dilon 6800 because they didn’t have a breast MRI package in their scanner. He said that they later upgraded, and now can do breast MRI, however they rarely find a need for it.

“MRI of the breast is very sensitive and a lot of lesions get picked up,” said Ravipati. “We have to sort out what is important, what is not. MBI is cheaper, more accurate, easy to use, and more definitive.”

BSGI is currently used on a minority of patients in clinics with the technology. Ravipati estimated that he performs BSGI on less than 10 percent of patients post-mammogram, to look at a potential lesion or if the patient’s breasts are dense and he’s not sure the mammogram was effective. Ward said that in her practice, some patients undergo multiple scans, but overall they use the BSGI in less than 2 percent of their patients.

While many doctors say BSGI is great at detecting hot spots of possible cancer, the radiation exposure is currently too high for general screening. Ward’s facility is participating in a study to see how lowering the dose will impact the sensitivity and specificity. “Hopefully we will find that the dose can be lowered to a level that will make this an acceptable screening tool,” she said. “Currently, BSGI is not a screening tool and should not be used as such. It’s more of a problem-solving tool when mammograms and ultrasounds are not definitive.”

Ward said the indications are similar as for MRI: to evaluate mulitfocality and multicentricity in women with a known diagnosis of breast cancer and for the monitoring of the response to neoadjuvant chemotherapy. Also, some patients would rather undergo BSGI than wait for a six month recall for a repeat mammogram.

PEM is also a nuclear breast imaging modality - it’s a PET scan specifically for breasts, using the tagged glucose, FDG. PEM can detect breast tumors as small as 2 mm in diameter, and can also be used as an alternative for breast MRI. However, insurance companies only pay for PEM for those with a known diagnosis of breast cancer. “It’s used to look for multifocality, multicentricity, and to evaluate the other breast for an occult cancer,” Ward said.

Another emerging technology is the recently-introduced whole breast ultrasound, manufactured by U-Systems. (Read more about whole breast ultrasound here.) This no-dose examination has been well received technologically, but reimbursement processes are lagging. As far as mammography advancements, 3-D mammography technology has emerged as a new promising tool that could significantly enhance diagnosis. Hologic Inc.’s Selenia Dimensions System received FDA approval to sell its 3-D system in the U.S. in February. A study showed that radiologists improved their ability to discern cancerous lesions from noncancerous ones by 7 percent, using 3-D versus 2-D images alone.

BSGI Learning Curve

Some physicians who have used BSGI report that there’s a learning curve to reading the scans, because false positives can be an issue, according to Ward and Ravipati. “You do get some false positives,” said Ward, noting that her facility has performed more than 1,000 cases. “We know this because many of these patients have undergone core needle biopsies and we have pathology. As with MRI, we have seen that there’s some proliferative changes in breast tissue that will be positive on BSGI. The BSGI is interpreted in conjunction with the mammogram and ultrasound; it is not a ‘stand alone’ test. You learn what your false positives are, and just like any modality, MRI included, you biopsy what you think is suspicious.”

The false positives in BSGI are often patchy areas of increased activity, Ward said. “Maybe the patient is premenopausal, and has a lot of changes related to hormone fluctuation. It’s not grossly positive.” Both she and Ravipati said they schedule premenopausal patients for early in their menstrual cycles in order to decrease or eliminate false positives.

If there are increased or “hot” areas on the BSGI scan, but other imaging studies are negative, Dr. Ward has the patient return in six months for a follow-up scan. Ravipati said he’ll often do a focused ultrasound with a traditional ultrasound machine, narrowing in on the suspicious area.

The flip side is that if the BSGI is negative, physicians trust the results. “The MBI scan is almost 100 percent accurate in terms of negative predictive value,” Ravipati said. “If the clinical situation isn’t clear and the MBI was negative, the biopsy was negative, you’re okay. You don’t need to pursue it any further.”

It’s not just the radiologists who find the technology helpful, it’s also the breast surgeons, said Crane, the KLAS researcher. “We saw a lot of positive comments from breast surgeons. They love the image quality it’s able to supply. A couple of them said it’s as crisp and clear a breast image as they’d ever seen,” she said.

The KLAS report showed that 86 percent of those surveyed would buy the Dilon 6800 MBI scanner again, and 7.2 out of 9 feel they’re getting their money’s worth.

“We were skeptical when we started, that it would be useful,” said Ravipati. “In the two and a half years we’ve had it, we are very, very happy and are kind of surprised that the rest of the country hasn’t caught up with it. MBI is a much simpler, easier to use, easier to read modality. It’s a very accurate examination. We’d like to see the other centers use it, rather than relying just on MRI.”