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New study shows, new breast cancer imaging methods that are being marketed as problem-solving adjunctive tools and "second-look" devices carry much higher radiation risks than mammography.

The risks reported are theoretical, but they should be communicated to patients as part of the process of obtaining informed consent, says the author, Edward Hendrick, PhD, from the Department of Radiology at the University of Colorado–Denver, in Aurora.

The new methods are breast-specific gamma imaging (BSGI) and positron emission mammography (PEM), both of which have been recently approved for use in the United States. They are marketed as diagnostic adjuncts to mammography and breast ultrasound, Dr. Hendrick explains. But they can also be considered for breast cancer screening, particularly in women at higher risk for breast cancer, he adds.

However, the radiation involved in a single BSGI examination poses a risk that is 20 to 30 times greater than that from digital mammography in a woman 40 years of age, and the risk from a single PEM screen is 23 times higher.

Undergoing 1 of these examinations — with either BSGI or PEM — has a lifetime risk of inducing fatal cancer that is greater than, or comparable to, a lifetime of annual mammography screening in women starting at 40 years of age, the author concludes.

To put radiation doses into some perspective, Dr. Hendrick explains that the average dose of natural background radiation that a person in the United States is exposed to is about 3 mSv per year.

The average "effective dose" from mammography (the whole-body dose with the same detriment) is around 0.44 to 0.56 mSv, which is equal to about 2 months of natural background radiation; the effective doses from BSGI and PEM (6.2 to 9.4 mSv) are equal to approximately 2 to 3 years of natural background radiation exposure.

The reason for the big difference is that the new methods involve intravenous injections of radioisotopes, which expose all organs of the body to gamma ray emissions, whereas mammography with lower-energy x-rays exposes only the breasts.

Not Suitable For Screening

The main message from this study to clinicians who are contemplating using these new imaging methods is that BSGI and PEM — as currently used — are not suitable for screening for breast cancer in healthy women, Dr. Hendrick told Medscape Medical News. They should be used prudently in all women, especially younger women (under the age of 40), because younger women are inherently more radiosensitive than older women, he added.

"BSGI and PEM should not be used for screening because of the higher risk of cancer induction, compared with existing modalities such as mammography, breast ultrasound, and breast magnetic resonance imaging ( MRI )," he says.

Currently, these new methods are being used for diagnostic evaluation after mammographic or physical detection of a suspicious finding, Dr. Hendrick explained. They are also used to evaluate the extent of disease when a woman has a biopsy-proven breast cancer. In such cases, the use of these new tests would have a different benefit-to-risk ratio, since the additional information obtained with the new imaging methods can "better guide treatment," he added.

These new methods are not currently being used for breast cancer screening, he notes, but he points out that there "has been talk" about using them (particularly BSGI) for screening women who are at high risk or who have dense breasts.

"But there are no scientific clinical studies to support that use," he asserts. "And much of that talk was before the radiation risks of these nuclear medicine studies were fully understood."

In fact, he adds, the radiation risks might be even higher in the populations suggested as targets for these new methods, because women who are genetically at high risk for breast cancer and women with dense breasts, who are more likely to be younger, are more radiosensitive than normal-risk and older women.

Dr. Hendrick, who acknowledges that there is "continuing controversy" over the best method to screen for breast cancer in women with different risks and ages, suggests that screening should be carried out with mammography for women who are 40 years and older. Women who are at high risk for breast cancer and younger than 40 years should undergo screening with breast MRI or ultrasound, whereas those at high risk and older than 40 years should undergo screening with some combination of mammography and breast MRI, probably annually, but staggered so that the tests are 6 months apart, he said.

"We know from randomized clinical trials that mammography has a mortality benefit," Dr. Hendrick said. "And from studies in high-risk women, we know that breast MRI is better than mammography in detecting cancers and evaluating the extent of disease; in high-risk dense-breasted women, we know that screening with ultrasound adds to mammography in terms of cancer detection."

In contrast, he pointed out: "we know very little about BSGI and PEM, except in relatively small studies (a few hundred subjects) of highly cancer-enriched study groups (e.g., those already identified as having lesions suspicious for breast cancer)."

Approached for comment, Valerie Jackson, MD, FACR, professor of radiology at the Indiana University School of Medicine in Indianapolis, told Medscape Medical News that "there is a great deal of research being done on BSGI and PEM, but neither are widely used. We are not doing any at [Indiana University], largely because we feel it does not add much, if anything, to our current methods for screening and diagnosis. We rely on mammography, breast ultrasound, and breast MRI. These modalities have been more fully investigated and have sound clinical indications."

Different Use of Radiation

The new imaging methods use radiation in a completely different way, Dr. Hendrick explains. Mammography uses external-beam low-energy x-rays (average energy, ~20 keV ), whereas the new methods use internally administered high-energy gamma rays (average energy, 140 keV for BSGI and 511 keV for PEM).

In addition, the new imaging methods use injected radioisotopes — BSGI uses technetium 99m (99mTc) sestamibi, which is also used in cardiac stress tests, and PEM uses fluorine 18fluorodeoxyglucose (FDG), the same as whole-body positron emission tomography scans for detecting metastatic cancer.

The distribution of these radionuclides in the bloodstream, their uptake into tissues, and their clearance in the liver (for 99mTc used in BSGI) and kidney (for FDG used in PEM) result in radiation exposure of organs in the chest, abdomen, and pelvis, Dr. Hendrick points out. The highest risk is to the colon in BSGI and the bladder in PEM.

The organs receiving the highest doses and therefore at greatest risk for cancer induction from radionuclide administration are the colon, lungs, and bladder. Cancers occurring in these organs are less curable than breast cancer, so the risk ratios for BSGI and PEM, compared with mammography, are greater for cancer mortality than for cancer incidence, he notes.

However, all of these radiation risks are theoretical, because there is no direct evidence that exposures at the level of mammography, BSGI, PEM, or computed tomography exams can cause an increase in cancer incidence or cancer deaths, Dr. Hendrick explains.

"We do know that much higher levels of radiation exposure, such as that received by survivors of the atomic bomb explosions at Hiroshima and Nagasaki, cause higher levels of cancer incidence and cancer deaths," he told Medscape Medical News.

"The theoretical part is that we extrapolate these high-level exposures to low-level exposures using a linear no-threshold model, which is generally viewed to be the most prudent approach for radiation protection (and is best supported by the existing data)."

Need for Greater Awareness of Radiation Risks

Wendie Berg, MD, PhD, FACR, breast imaging radiologist in Lutherville, Maryland, who was also approached for comment, told Medscape Medical News that she agrees with Dr. Hendrick's conclusions and comments.

"There is a need for greater awareness of the amount of radiation used in any medical imaging test, and the relative risks," she said.

"For mammography, that risk is extremely low, and far less than the benefit in lives saved by detection of early breast cancer," she said.

But mammography does not catch all breast cancers, especially in women with dense breasts, she pointed out. Two other methods, MRI and ultrasound, do not use any ionizing radiation at all, but each has problems. "MRI is very expensive and not well tolerated by all women, and ultrasound is limited by a shortage of trained personnel and a large number of false positives," she said.

Thus, there is interest in other approaches to supplement mammography. "For nuclear medicine approaches to be considered for breast cancer screening, the benefits in early detection of cancer need to outweigh the risks from radiation," Dr. Berg said.

She agreed with Dr. Hendrick that PEM and BSGI — as he described in his paper — are not suitable for screening because of the high doses of radiation used. But she added that there is another molecular breast imaging approach, in which the radiation dose has been greatly reduced, which does hold promise.

Dr. Berg explained that there are 2 different systems for imaging 99mTc sestamibi in the breasts. One of the systems, BSGI (Dilon Technologies), uses a single detector and doses of 20 to 30 mCi; this is the system that Dr. Hendrick used in his calculations, she explained. "This system has been used in some institutions for problem solving when a woman cannot tolerate an MRI," she explained, and agreed it should not be used for screening at these doses.

But there is a gamma camera system (from Gamma Medica-Ideas) that uses dual detectors and special collimators and much lower doses (2 to 4 mCi), which are comparable to the radiation dose of 1 or 2 mammograms, she explained. This system needs more study, but it "appears to have great potential for screening women with dense breasts," she said.

Dr. Berg added that she has been involved in clinical trials with PEM (Naviscan), which is used in women with known breast cancer to plan treatment. In this case, the benefit to proper treatment exceeds the risk for radiation from PEM, she said, although she added that "we can likely cut the dose from PEM in half."

Source: RSNA