A new technique combines imaging and mathematics to identify aggressive forms of ductal carcinoma in situ (DCIS), or stage 0 breast cancer, from nonaggressive varieties. The technique is known as biomarker ratio imaging microscopy (BRIM).1

“A patient with DCIS is typically treated as if she has invasive disease, which is easy to understand. When women hear breast cancer, they’re petrified. And physicians are keenly concerned about outcomes as well,” said Howard R. Petty, PhD, professor of ophthalmology and visual sciences and of microbiology and immunology at the University of Michigan Medical School, Ann Arbor, and study author.

“But, DCIS is not the same disease for everyone. If we can identify potentially non-aggressive lesions, perhaps those women don’t need aggressive treatment.”

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BRIM fuses traditional pathology techniques with mathematical analysis to determine the relative levels of certain biomarkers in a tumor. This study looked at biopsy samples from 23 patients with DCIS. They used fluorescence imaging, in which tumors are stained to identify key biomarkers. Each biomarker was stained a different color. The stained samples were then entered into a computer program that determines the ratio of biomarker in each pixel.

Some biomarkers are highly expressed in cancer; others have very low expression. With BRIM, researchers take the ratio of expression. This means high and low do not cancel each other out, but rather combine to form an image of improved contrast.

The technique allowed the researchers to separate the DCIS patient samples based on which had a high portion of cancer stem cells; more than one-fifth (22%) had low scores suggestive of very slow-growing, nonaggressive disease.

“This approach is going to be a new and powerful one. It works because we’re looking at it mathematically,” Petty said. Though common screening mammography has increased the rates of DCIS, there is not currently a way to stratify the disease based on aggressiveness.

The researchers suggest that in addition to preventing overtreatment, BRIM could be used to help more broadly with breast cancer treatment decisions. As the biomarker literature becomes more expansive in other cancer types, the researchers say they will expand their work to other forms of cancer.

A large retrospective study correlating BRIM scores to patient outcomes is planned.


1. Clark AJ, Petty HR. Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy. Scientific Reports. 2016;6:27039. doi: 10.1038/srep27039.