Finding the Smallest Cancers Ever Detected

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A new magnetic resonance imaging procedure can spot breast cancer very early in mice, finding the smallest cancers ever detected by MRI.

Some of the tumors were less than 300 microns in diameter (a single red blood cell, by comparison, is about 7 microns across), and the new MRI also detected ductal carcinoma in situ (DCIS), a precursor to invasive cancer.

Researchers hope the new technique will aid their understanding of DCIS, helping to differentiate between tumors that will become invasive cancers and require surgery, and those that will not. It will also be used to measure the impact of various preventive therapies, such as green tea, on tumor development.

As researchers from the University of Chicago Medical Center report in the Sept. 9, issue of Physics in Medicine and Biology: “These experiments provide proof of principle that microscopic mammary tumors can indeed be detected and followed in a mouse model of breast cancer.”

“These are very small tumors,” added cancer specialist and study co-author Suzanne Conzen, MD, associate professor of medicine at the University of Chicago Medical Center. “They are much too small to feel or even to see without a microscope.”

Ductal carcinomas in situ make up about 20 percent of newly diagnosed breast cancers, and have the best prognosis, with long-term survival rates between 97 and 99 percent. Although MRI is already used as a screening tool, more sensitive tests that could detect cancers earlier, during more treatable stages, could boost survival rates.

“We decided to try to push the technology a step or two,” said Greg Karczmar, professor of radiology and medical physics at the University of Chicago Medical Center, “to see if we could get good pictures of something people didn’t believe could be imaged.”

The key was the development of a special “birdcage” coil for MRI of the mouse mammary glands, and the team began testing a wide range of protocols to get images that could distinguish between cancer, normal breast tissue and fat.

They found that, when optimal methods were employed, both DCIS and early invasive tumors “appeared clearly against a darker background.” In 12 mice, MRI was able to detect the one relatively large tumor, 17 out of 18 small tumors that were smaller than a millimeter, and 13 out of 16 milk ducts that were distended with carcinoma in situ, including some tumors less than 300 microns in width, about one-third of a millimeter. Just as important, there were no false positives.

Unlike previous MRI studies of tumors in mice, the researchers were able to detect very small naturally occurring cancers, which were excellent models for human breast cancer; the tumors the mice developed were “realistic models of the most frequently detected human cancers,” the authors wrote. “The morphology of these early murine mammary cancers on MRI is similar to the MR presentation of early human breast cancer.”

The National Institutes of Health, the Department of Defense, the Segal Foundation, the Florsheim Foundation and the University of Chicago Cancer Research Center supported the research.

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