Low-Dose Molecular Breast Imaging: Is It Finally Here?
Sponsored by an educational grant from Gamma Medica
Breast cancer results in approximately 460,000 deaths globally each year, including 40,000 women in the U.S. Breast cancer is the leading cancer killer among women aged 40 to 59 years in high-income countries, according to the World Health Organization. While mammography screening has been shown to reduce mortality, its sensitivity is greatly reduced in women with dense breasts. Low-dose molecular breast imaging (MBI) holds promise as an inexpensive alternative for these patients.
While mammography is the gold standard for breast cancer detection, the sensitivity of mammography is reduced in dense breasts, with sensitivity estimates of extremely dense breasts ranging from 30 to 63 percent (Radiology 2002;225[1]:165-175).
How large is the dense breast population? "There is an old saying: About 80 percent of women at age 40 have dense tissue, and approximately 40 percent of women at age 80 have dense tissue," explains Michael K. O'Connor, PhD, professor of medical physics in the nuclear medicine section at Mayo Clinic in Rochester, Minn. "Of the average population who gets screening mammography, about 25 to 30 percent would be considered to have at least D3 or D4 breasts."
Breast density is categorized from D1 up to D4, with D1 being primarily fatty, adipose tissue, while D4 contains extremely dense fibroglandular tissue in the breasts. "The D3 and D4 population are the women in which we are concerned that mammography may not detect their cancers. That's about 30 percent of the screening population" O'Connor says.
Also, women with dense breast tissue have a higher risk of getting cancer, compared with those who have more fatty breast tissue, by about a factor of four to six, according to O'Connor. "Unfortunately, in a D4 breast, the sensitivity in mammography drops to between 25 and 35 percent," he adds.
O'Connor and his colleagues at Mayo have previously compared the performance of dual-head, CZT-based gamma imaging with mammography in screening women with mammographically dense breasts (Radiology 2011;258[1]:106-118). In this study of 936 participants, led by Deborah Rhodes, MD, 11 had cancer (three detected by mammography, nine by gamma imaging, and one by neither). Diagnostic yield was 3.2 per 1,000 for mammography and 9.6 per 1,000 for gamma imaging.
The authors concluded that the addition of gamma imaging to mammography "significantly increased detection" of node-negative breast cancer in dense breasts by 7.5 per 1,000 women screened. However, they added that to be "clinically important, gamma imaging will need to show equivalent performance at decreased radiation doses."
MBI studies currently use the radiotracer Tc-99m sestamibi, which is an FDA-approved agent for breast imaging. As with any imaging technique, the goal is to use the lowest possible dose that has been clinically proven to achieve the desired clinical benefit.
The original MBI studies were performed with a dose of 20 mCi of sestamibi, which is equivalent to the radiation dose of five to 10 mammography exams. Thus, the Mayo team spent three years working on a variety of technical enhancements to MBI to reduce the dose, without negatively impacting the quality of the study. "Now, images acquired at 8 mCi with our current technology are better than the original images acquired at 20 mCi, and exams using 4 mCi are nearly equivalent in quality to the 20 mCi images," says O'Connor.
"We are still working with various software algorithms to achieve an additional level of image enhancement. With the most recent algorithm, we believe that the images at a 4 mCi dose are essentially equivalent to images with the current 8 mCi," says O'Connor.
A larger study sponsored by the Komen Foundation, is currently underway screening 2,400 women with dense breasts at a low dose of 8 mCi Tc-99m sestamibi. The much-anticipated interim results of this study will be presented at RSNA 2011 (Nov. 28, 9:30am).
Based on these findings, Robin B. Shermis, MD, MPH, medical director of Toledo Hospital Breast Care Center in Ohio, and his team are on the verge of reducing their MBI exams from 8 mCi to 4 mCi. "Once you reach that 4 mCi dose, it is basically the radiation level of a mammogram," Shermis says. "With this technology, we are uncovering cancers as small as 5 mm."
About 15 percent of women for whom MRI is indicated, do not undergo the procedure for various reasons, such as a having pacemaker, obesity, they can't lie down for the required period of time, they are claustrophobic or they have renal problems. "These women should have an MRI, but it cannot be done. Until we started molecular breast imaging, there was no recourse. Also, remember, in some areas of the country, breast MRI is not available," Shermis says.
"Fifteen percent is not a insignificant number when these women are at high risk or otherwise recently diagnosed with cancer. MBI is a helpful fall-back technology to screen high-risk patients as well as for preoperative planning, if MRI is not possible."
Breast cancers, even large ones, can be obscured on a complex dense mammogram. At the Toledo Hospital, women who do not qualify for MRI by risk level can obtain additional surveillance with MBI with the goal of catching cancers at an early stage.
"We have benefitted from utilizing [MBI], which has a comparatively small radiation dose, and is relatively inexpensive," says Shermis, who adds that Medicare reimbursement is approximately $400 to $500 per exam.
"In today's healthcare environment, every technology must not only prove its clinical worth, but also its fiscal worth," he adds.
At Mayo, the difference in price is about a factor of seven with MBI being that much less expensive than MRI, O'Connor explains.
With the advent of low-dose techniques, the next step may be to use MBI as a secondary screening technique to mammography, as opposed to MRI. This is the focus of ongoing work at Mayo.
"We think this technique would be very valuable in women for whom mammography is not the best choice," O'Connor concludes. "While the industry evaluates this new supplemental tool as the best solution for women with dense breasts, the inexpensive nature of this test, the published clinical benefits, the ease of interpretation for the breast specialist and now a lower dose molecular breast imaging solution could potentially support the argument."
Breast cancer results in approximately 460,000 deaths globally each year, including 40,000 women in the U.S. Breast cancer is the leading cancer killer among women aged 40 to 59 years in high-income countries, according to the World Health Organization. While mammography screening has been shown to reduce mortality, its sensitivity is greatly reduced in women with dense breasts. Low-dose molecular breast imaging (MBI) holds promise as an inexpensive alternative for these patients.
A solution for dense breasts
Molecular breast imaging is a nuclear medicine technique that utilizes semiconductor-based gamma cameras in a mammographic configuration to provide high-resolution, functional images. The LumaGEM Low Dose MBI System (Gamma Medica) is the first commercially available, planar, dual-head, solid-state digital detection system utilizing cadmium zinc telluride (CZT) used for breast imaging.While mammography is the gold standard for breast cancer detection, the sensitivity of mammography is reduced in dense breasts, with sensitivity estimates of extremely dense breasts ranging from 30 to 63 percent (Radiology 2002;225[1]:165-175).
How large is the dense breast population? "There is an old saying: About 80 percent of women at age 40 have dense tissue, and approximately 40 percent of women at age 80 have dense tissue," explains Michael K. O'Connor, PhD, professor of medical physics in the nuclear medicine section at Mayo Clinic in Rochester, Minn. "Of the average population who gets screening mammography, about 25 to 30 percent would be considered to have at least D3 or D4 breasts."
Breast density is categorized from D1 up to D4, with D1 being primarily fatty, adipose tissue, while D4 contains extremely dense fibroglandular tissue in the breasts. "The D3 and D4 population are the women in which we are concerned that mammography may not detect their cancers. That's about 30 percent of the screening population" O'Connor says.
Also, women with dense breast tissue have a higher risk of getting cancer, compared with those who have more fatty breast tissue, by about a factor of four to six, according to O'Connor. "Unfortunately, in a D4 breast, the sensitivity in mammography drops to between 25 and 35 percent," he adds.
O'Connor and his colleagues at Mayo have previously compared the performance of dual-head, CZT-based gamma imaging with mammography in screening women with mammographically dense breasts (Radiology 2011;258[1]:106-118). In this study of 936 participants, led by Deborah Rhodes, MD, 11 had cancer (three detected by mammography, nine by gamma imaging, and one by neither). Diagnostic yield was 3.2 per 1,000 for mammography and 9.6 per 1,000 for gamma imaging.
The authors concluded that the addition of gamma imaging to mammography "significantly increased detection" of node-negative breast cancer in dense breasts by 7.5 per 1,000 women screened. However, they added that to be "clinically important, gamma imaging will need to show equivalent performance at decreased radiation doses."
MBI studies currently use the radiotracer Tc-99m sestamibi, which is an FDA-approved agent for breast imaging. As with any imaging technique, the goal is to use the lowest possible dose that has been clinically proven to achieve the desired clinical benefit.
The original MBI studies were performed with a dose of 20 mCi of sestamibi, which is equivalent to the radiation dose of five to 10 mammography exams. Thus, the Mayo team spent three years working on a variety of technical enhancements to MBI to reduce the dose, without negatively impacting the quality of the study. "Now, images acquired at 8 mCi with our current technology are better than the original images acquired at 20 mCi, and exams using 4 mCi are nearly equivalent in quality to the 20 mCi images," says O'Connor.
"We are still working with various software algorithms to achieve an additional level of image enhancement. With the most recent algorithm, we believe that the images at a 4 mCi dose are essentially equivalent to images with the current 8 mCi," says O'Connor.
A larger study sponsored by the Komen Foundation, is currently underway screening 2,400 women with dense breasts at a low dose of 8 mCi Tc-99m sestamibi. The much-anticipated interim results of this study will be presented at RSNA 2011 (Nov. 28, 9:30am).
Based on these findings, Robin B. Shermis, MD, MPH, medical director of Toledo Hospital Breast Care Center in Ohio, and his team are on the verge of reducing their MBI exams from 8 mCi to 4 mCi. "Once you reach that 4 mCi dose, it is basically the radiation level of a mammogram," Shermis says. "With this technology, we are uncovering cancers as small as 5 mm."
MBI in clinical practice
Physicians at Toledo Hospital, which conducts more than 40,000 breast cancer screening exams annually, suggest that there are two patient populations who can benefit from low-dose MBI: High-risk women and those with a recent diagnosis of breast cancer who cannot have or tolerate MRI; and secondly, women in the general population who have a complex dense (difficult to interpret) mammogram, but do not qualify for MRI.About 15 percent of women for whom MRI is indicated, do not undergo the procedure for various reasons, such as a having pacemaker, obesity, they can't lie down for the required period of time, they are claustrophobic or they have renal problems. "These women should have an MRI, but it cannot be done. Until we started molecular breast imaging, there was no recourse. Also, remember, in some areas of the country, breast MRI is not available," Shermis says.
"Fifteen percent is not a insignificant number when these women are at high risk or otherwise recently diagnosed with cancer. MBI is a helpful fall-back technology to screen high-risk patients as well as for preoperative planning, if MRI is not possible."
Breast cancers, even large ones, can be obscured on a complex dense mammogram. At the Toledo Hospital, women who do not qualify for MRI by risk level can obtain additional surveillance with MBI with the goal of catching cancers at an early stage.
"We have benefitted from utilizing [MBI], which has a comparatively small radiation dose, and is relatively inexpensive," says Shermis, who adds that Medicare reimbursement is approximately $400 to $500 per exam.
"In today's healthcare environment, every technology must not only prove its clinical worth, but also its fiscal worth," he adds.
At Mayo, the difference in price is about a factor of seven with MBI being that much less expensive than MRI, O'Connor explains.
With the advent of low-dose techniques, the next step may be to use MBI as a secondary screening technique to mammography, as opposed to MRI. This is the focus of ongoing work at Mayo.
"We think this technique would be very valuable in women for whom mammography is not the best choice," O'Connor concludes. "While the industry evaluates this new supplemental tool as the best solution for women with dense breasts, the inexpensive nature of this test, the published clinical benefits, the ease of interpretation for the breast specialist and now a lower dose molecular breast imaging solution could potentially support the argument."