Digital breast tomosynthesis shows promise in catching more cancers and reducing false-positives. Wider testing might bear that out, but won’t happen until the technology gains FDA approval. Therein lies the catch.

Daniel B. Kopans, MD, read an article 32 years ago about a technique of layering multiple x-rays to create a three-dimensional image of a part of the human body. Kopans, now known as one of the world’s leading experts in breast imaging, was at the time division head of xeroradiography at Massachusetts General Hospital (MGH) and saw great potential for using this technique—tomosynthesis—in mammography.

Kopans and a team of physicists at MGH won a patent for digital breast tomosynthesis (DBT) and worked with General Electric to build the first DBT device that could image the entire breast. Over the last two decades, Kopans has read more than 3,000 DBT images, written extensively about the benefits of tomosynthesis, and worked with other manufacturers, including Hologic and Siemens, to advance as he calls it, “the art and science” of the technology.

But look in just about any imaging center, and about the only thing you’ll find on DBT is in a journal article resting on a table in the waiting room. Manufacturers have been guarded about development, and the US Food and Drug Administration has been characteristically unhurried.

“The FDA is very concerned about making a mistake with breast cancer,” said Kopans, who earned his MD from Harvard Medical School where he is now a professor of radiology. “It is one of the most visible of diseases and the public is very involved. It is not surprising that they are being very cautious with DBT.”

Not surprising, but still frustrating for advocates of the technology like Martin Yaffe, PhD, a senior scientist in imaging research at Toronto’s Sunnybrook Health Sciences Centre and Tory Family Chair in Cancer Research and professor in the departments of Medical Biophysics and Medical Imaging at the University of Toronto. Yaffe sees breast tomosynthesis as “the next logical step” in digital mammography.

“The bar that’s been set for approval of tomosynthesis is ridiculously high,” Yaffe said. “When you have a new technology, really the role of a regulatory agency is to see that it’s safe and the role of the academic community is to review its effectiveness—the only way you find out is by using it. That’s not what’s happening with tomosynthesis. There are a few prototype systems being used in trials by manufacturers who are seeking regulatory approval. My sense is the manufacturers are very nervous about publishing findings. Anything that is less than completely positive might detract from getting approval.”

Bedford, Mass-based Hologic, which has been at the fore of DBT development dating back to Kopans’ early work at Massachusetts General, illustrates well the lengthy process to gain approval. The company announced a September 2010 review of its Selenia Dimensions three-dimensional digital mammography tomosynthesis system by the FDA’s Radiological Devices Panel—part of a premarket approval application (PMA) filed in 2008.

Part of the issue, Yaffe said, may be the lack of large studies on breast tomosynthesis, particularly in the United States. The technology has won approval in Europe and Canada. “In the United States, breast imaging is already doing well, so in order to show improvement, you have to do pretty large studies. To be big enough, it’s got to be multi-institutional, and we haven’t seen studies like that. We are working on research in tomosynthesis systems, but certainly we’re not in a position to publish large studies ourselves. We’re one of a group of centers that’s working on clinical evaluation.” Much of that work is being done as part of the FDA approval process.

A Clearer Edge

Interpreting mammograms, whether film or digital, is like looking at a book with clear pages; the words are superimposed and difficult to read. Kopans said tomosynthesis allows the radiologist to page through the breast, eliminating confusion from superimposition of tissues and presenting a clearer image of lesions. “The 3D location of the lesion is never in doubt and we do not call women back for what prove to be superimposed normal tissues. In other words, many of the reasons to recall a woman from screening are eliminated.”

Yaffe estimates 10% of examinations lead to a recall. “They’re not clearly enough negative that you can send the patient home so you have to do further testing. And most of those women don’t have cancer—five in 1,000 will have it. If you can reduce that false-positive rate, you’re reducing all that stress in those women you call back, reducing the costs of all the workup exams.”

Hologic?s Selenia Dimensions Breast Tomosynthesis System is awaiting FDA clearance.

The available research on tomosynthesis shows those false positives can be reduced by approximately 40%. Beyond that, the technology has:

  • Generally favorable patient acceptance;
  • Reads in about the same time as standard mammography;
  • Detection of additional cancers that are missed on two-dimensional mammograms;
  • Clearer margins of a lesion (used to determine its importance) than 2D; and
  • Improved localization.

“Once the FDA permits the sale of these devices, the benefits will become very clear,” Kopans said. “The x-ray companies do not have unlimited resources to distribute DBT devices to get wider clinical experience. This will only happen with FDA approval. My experience suggests that it will be rapidly accepted, and that cancers that would have been missed on 2D will be detected by DBT while the false-positive rate will decrease.”

But as Kopans acknowledged, first comes approval. Mark A. Helvie, MD, professor of radiology and director of breast imaging at the University of Michigan Health System, Ann Arbor, said in a 2009 Axis Imaging News article on breast tomosynthesis, nothing has been conclusive—at least not yet. “Although early research has shown that false-positive rates decrease with the use of breast tomosynthesis, actual use may bear out less rosy numbers. In a clinical situation, the intensity with which clinicians pursue a mass may be greater than in a research situation. A 1% or 2% risk in research may not bother you, but in a clinical situation, you may be required to further evaluate that lesion,” Helvie said.

Part of the reason Kopans believes adoption will come quickly after FDA approval is that the more precise imaging process doesn’t require a lot of new training for imagers.

“These are still x-ray images so that the radiologist does not need to learn new descriptors,” Kopans said. “It becomes fairly easy. There is nothing to prevent a radiologist from having the 2D images as well—the DBT devices are just modified 2D digital mammography units. This is the basis for Hologic’s PMA request. Once they become comfortable, the advantages outweigh the disadvantages, and since the positioning is the same, a technologist need be skilled only in mammography.”

Yaffe goes so far as to say breast tomosynthesis has the potential to replace digital mammography as a screening tool. “I think the ability to reduce that false-positive rate is very important and there’s economic impact to finding cancers that are currently missed.”

In a health care world of constant development and improvement, Yaffe said the industry standard in another decade could be completely removed from x-ray imaging, but in the meantime, tomosynthesis makes an incremental improvement.

“I think potentially it’s a great technology,” he said. “I need to see the proof myself, even though I’m excited about it. We may find that tomosynthesis is not superior to everything. We may find it’s very good for a certain range of tasks. We just don’t have all the results. We could be getting those results much more quickly in a different environment.”

Dan Anderson is a contributing writer for Axis Imaging News.