Molecular Breast Imaging: When to Use It

There is good news and bad news with breast cancer. While incidence rates have decreased by 2 percent per year between 1999 and 2006 and breast cancer death and diagnosis have largely declined because of improved screening and training techniques, current imaging methods have fallen short on detecting the disease effectively and early in certain patient populations. These specific patient populations include women found to have dense breast tissue.

According to the American Cancer Society (ACS), dense breast tissue is one of the top risk factors for breast cancer.  Breast tissue density is a measure of glandular tissue relative to fatty tissue.  Approximately 40 percent of all women have dense breast tissue with the largest population being under the age of 50.   According to the ACS, this particular group of women that have the highest levels of breast density have a 4 to 6 fold increased risk of developing breast cancer compared with other women.

In 2010, an estimated 207,090 new cases of invasive breast cancers and 54,010 cases of non-invasive in situ breast cancers will be diagnosed.  Here’s some good news: A better mousetrap—Molecular Breast Imaging—is now ready for imaging high-risk women.

Molecular Breast Imaging (MBI) brings the advantage of functional imaging that can overcome the limitations of anatomic imaging.  Researchers from the Mayo Clinic in Rochester, Minn., are using MBI, a technique that uses the LumaGEM Molecular Breast System by Gamma Medica, Inc. of Northridge, CA.  The LumaGEM is the first commercially available, FDA cleared, planar, dual-head, fully solid state digital imaging system utilizing cadmium zinc telluride (CZT) technology used for breast imaging.  Commercial shipments of the system in the U.S. began this past year. A system has already been sited in Italy as well.

Mayo Clinic is the epicenter of MBI, spearheading 14 MBI research-based projects that have collectively studied more than  2,500 patients. The studies have looked at MBI in patients presenting for surgery without breast cancers, those with atypical breast lesions and assessed the technology to screen women with dense breast tissue. Research published in 2008 found that MBI surpasses mammography in the detection of invasive ductal carcinoma, ductal carcinoma in situ and invasive lobular carcinoma [Am J Surg 2008; 196(4):470-6].

Since then, MBI has been found to be three times more sensitive at identifying breast cancers when compared to mammography (it has since matched that performance compared to MRI). When a single-head LumaGEM MBI System was used, sensitivity for breast cancer detection was 85 percent and 29 percent for tumors with a diameter of 5mm or less. With the new dual-head LumaGEM MBI System, detection rates jumped to 91 percent and 69 percent for tumors 5mm or less. Sensitivity to tissue abnormalities with diameters of 5 mm to 20 mm is 90 percent.

“While MBI is most comparable to breast MRI in that it exposes cancers that may not be identifiable with mammography or ultrasound, both modalities have their differences, some good and others bad,” says Michael K. O’Connor, PhD, of the department of Internal Medicine at Mayo Clinic. Breast MRI’s major advantage comes from the absence of radiation; however, O’Connor notes that MRI also produces false-positive findings that often lead to additional imaging tests. And while MBI requires radiation, it is five times less expensive than MRI and is a “far simpler technology to both install, use and maintain,” he notes.

Detection in dense breasts

Molecular breast imaging (MBI) has helped the staff at Mayo better detect tumors that are missed by mammography. This patient had a tumor missed on mammography but detected on MBI and confirmed by an ultrasound biopsy. The images were taken during Mayo’s low-dose MBI study and used 4 mCi of Tc-99m sestamibi rather than the usual dose of 25 to 30 mCi that is currently used by BSGI.

The majority of MBI research is currently studying the modality as a screening tool for dense breasted women.  “In this patient subset, mammography has demonstrated great difficulty while MRI has not yet been recommended due to its high costs and variable specificity,” says Carrie B. Hruska, PhD, associate consultant in medical physics in the department of Nuclear Medicine at Mayo.

In dense breast tissue, tumors are often buried or overlapped with dense tissue, says O’Connor. “In a situation where the breast is primarily fatty tissue, tumors are very easy to spot, so mammography does well with those patients.”  
Mayo research has shown that MBI detected three times as many cancers as mammography, results Hruska calls “statistically significant.”

Outside of screening, MBI is being looked at as a means of monitoring breast cancer therapy. A pilot project at Mayo is looking at MBI when performed before and after neoadjuvant chemotherapy administered before mastectomy. Results are promising, with Hruska noting that in dense-breast women they could accurately predict response to therapy compared to mammography.

“This is exciting and I really think MBI is going to be the right answer for women who have dense breast tissue,” says Deborah J. Rhodes, MD, of the Internal Medicine and Division of Preventive and Occupational Medicine at Mayo.

“We certainly don’t mean to suggest that MBI is going to replace mammography [for screening all women], but we would like to see it eventually be used as an individualized approach to breast cancer screening for certain patient subsets,” she says.

To determine if MBI would be a viable solution for screening women with mammographically dense breasts, a large study, the first of its kind, needed to be correctly conducted to prove the concept.  Should the results of such a study demonstrate that MBI was not an option, research would not need to go any further.  However, should the results clearly demonstrate the effectiveness of MBI as a supplemental screening tool in women with mammographically dense breasts, then the necessary and responsible next step would be to address the radiation dose.  

Newly published online November 2 (ahead of print), in Radiology (doi:10.1148/radiol.10100625) are the much-anticipated clinical results.  The study will be presented by Rhodes at the upcoming RSNA 2010 meeting in Chicago (presentation on Monday, November 29th at 8:55am, Aerie Crown Theater, CODE:  VM21-03).

Rhodes conducted a study of 936 at-risk women comparing mammography and dual-head MBI.  This study showed the sensitivity of mammography alone was 27 percent, while the sensitivity of combined mammography and MBI was 91 percent. In total, 11 breast cancer patients were screened and MBI detected nine of the 11 cancers while mammography only picked up three—making MBI three times as more sensitive as mammography.  “We hope to have different tiers of breast cancer screening depending on individual patient factors. That is really our goal,” says Rhodes.

Decreasing dose, increasing detection

While this MBI research showed clinical promise, imaging tests were performed at unfavorable levels of radiation, says O’Connor. Initial exams were delivering 20 millicures (mCi) of Tc-99m Sestamibi per exam. For diagnostic applications, these radiation doses may be lower than others currently on the market.  However, to prove itself as a screening tool, these doses are too high, O’Connor says.

Mayo Clinic is already fast at work reducing the dose by a ratio of five to 10 and still managing to furnish high-quality breast images. To do so, O’Connor and colleagues completed a physical redesign of the collimation of the MBI system that now allows a sensitivity ratio of two to three.

An even larger study, sponsored by the Komen Foundation, is currently well underway screening 2,500 general population women with dense breasts at a dose already as low as 4 mCi Tc-99m Sestamibi. This low-dose screening study having already enrolled almost 300 patients has already picked up three tumors with MBI, says O’Connor, none of which were picked up by mammography. He suspects that it will take about 12 months to validate whether or not the new low-dose protocols can detect tumors at similar image qualities and repeat the great clinical outcomes we have just seen with the Rhodes study.