Better Marker Devised for Breast Cancer May Reduce Need for Second Surgeries

Microscopic gas-filled spheres of silica, a porous glass, have been developed to tag the location of early-stage tumors to show their position using ultrasound imaging in the operating room.

A team of chemists, radiologists, and surgeons at the University of California, San Diego (UCSD; USA) created the new material, which they describe in a forthcoming issue of the journal MedChemComm. The X-rays utilized to make mammograms reveal calcium deposits associated with breast cancer even in tumors too small to be felt. However, surgeons cannot use X-rays while operating. Instead, radiologists place guide wires into tumors hours or even the day before surgery. Wires do not mark depth well and can shift; patients find them both uncomfortable and disquieting.

As an alternative, researchers created spheres of silica and filled them with perfluoropentane, a gas that has been used before in short-lived contrast materials for medical imaging. The rigid silica shells help the new material last longer. "These little gas-filled microbubbles stick to human breast tissue for days and can be seen with ultrasound,” said Dr. William Trogler, professor chemistry. "If doctors placed them in early stage breast cancer, which is difficult to see during surgery, they could help surgeons remove all of it in the first operation.”

In the past few years, radiologists have tried implanting radioactive "seeds” instead of wires to mark tumors, but the seeds last only a few hours and must be inserted with a large-bore needle, which is painful. In addition, only one abnormal region can be marked, but patients with a form of breast cancer called ductal in situ carcinoma often have several.

At just two micrometers in diameter, small silica microbubbles can be precisely injected into clusters of abnormal cells using a thin needle. Radiologists would be able to inject the durable material days before surgery. Moreover, ultrasound scans reveal the position of the bubble in three dimensions on the operating table. "Instead of just using a Geiger-counterlike device to say you're getting closer to the radioactive seed, you could actually see where to carve,” said Dr. Andrew Kummel, professor of chemistry. The optimal precision should help surgeons avoid the need for second surgeries.

"By outlining the tumor more completely in multiple directions, the particles could potentially help surgeons remove nonpalpable tumors in a single operation,” said Dr. Sarah Blair, a surgeon at Moores UCSD Cancer Center.

The researchers believe the ultrasound pressure waves burst the microbubbles. "They're thin, fragile balls of porous glass, like Christmas tree ornaments,” Dr. Kummel commented. "The shell is just one two-hundredth of the diameter of the ball. When it breaks, the gas squirts out. Doppler ultrasound detects that movement.”

Nanoscale silica microbubbles, which the investigators report in the article as well, are too small to remain in place, but might drain from a cancerous site to help identify which lymph nodes are most apt to contain errant cells that could help the cancer metastisize.

The current study demonstrates the viability of the technology in tissue samples. Tests in animal models are ongoing, and toxicology studies must also be completed before clinical trials in humans could begin.

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