Detecting and treating breast cancer is like a biological game of hide-and-seek. Clinicians must figure out whether a patient has cancer, how far the cancer has spread, and how much tissue to remove during surgery.
Precisely mapping tumors can translate into better outcomes. But cancer is good at this game. It knows how to evade detection, sometimes until it’s too late.
To overcome cancer’s advantages, researchers at UC Davis are developing advanced technologies to (sometimes literally) shine a light on tumors, differentiating malignant cells from normal tissue. Armed with these new approaches, clinicians will soon have better tools to seek out and destroy tumors, and improve the quality of life for breast cancer patients.
For women over 40, regular screening mammograms are an expected, albeit uncomfortable, inconvenience. The procedure can find small lumps and pre-cancerous calcifications that a self-exam might miss. Going one step further, diagnostic mammograms can help determine whether a suspicious lump is actually cancer.
But mammograms have limitations. They produce two-dimensional images of three-dimensional structures. This can be problematic, as normal glandular tissue and tumors have similar densities, giving cancer an opportunity to hide, particularly in women with dense breasts.
Researchers Ramsey Badawi and John Boone are working on a new system that could help — a small PET/CT scanner designed specifically to detect breast cancer. The scanner’s high resolution and three- dimensional capabilities could better differentiate between tumors and healthy tissue.
“The whole idea behind this scanner is to unobscure the radiologist’s ability to see a lesion by slicing through the breast,” says Boone, professor of radiology and biomedical engineering, who manages the CT side of the project. “You can look at the breast slice by slice and remove the underlying glandular tissue that might normally obscure the lesion.”
The positron emission tomography (PET) scanner makes the system even more powerful. Because malignant cells divide so rapidly, they tend to have bigger appetites. Patients are given an injection of a sugar tagged with a radioactive isotope. The radioactive sugar concentrates in hungry tumors, lighting them up for the PET scanner.
“You can really tell the difference between cancer and normal tissue,” says Badawi, chief of nuclear medicine. “If you have cancer and milk-producing tissue right next to each other, it can be difficult to tell them apart. With a PET scan you can see the cancer more clearly.”
Because the dual machine is built to detect breast cancer it must have high resolution, and each succeeding prototype has gotten better. With the current system, the PET can detect lesions as small as 1.2 millimeters, while the CT picks up calcifications as small as .1 millimeter. This technology could be especially useful for diagnostic imaging, determining if a lump is actually cancer. In addition, PET/CT could help oncologists track whether a treatment is working, giving them better data to make mid-course corrections.
Once cancer is confirmed, it needs to be eliminated. In many cases, women receive a lumpectomy, followed by additional chemotherapy or radiation. During lumpectomies, surgical teams work diligently to get every bit of the cancer.
Immediately after it’s removed, the tumor is sent to pathology and the outside cells closely examined. If pathologists find no cancer cells on the outer edge (negative margin), the procedure has been successful. However, if they do find cancer (positive margin), it’s likely there are still malignant cells in the body, and additional surgery may be necessary.
But what if surgeons had a simple device that could differentiate between malignant and normal tissue in real time? That’s the vision behind a device being developed by Laura Marcu, professor of biomedical engineering and neurological surgery. Using a technology called time-resolved fluorescence spectroscopy (TRFS), the device uses light to excite molecules in tissue and to measure how long they emit light of their own after they are excited. Different types of molecules emit light at different rates. TRFS can measure these rates, and identify malignant and healthy tissue.
“Using fiber optics to deliver and collect light, we can remotely characterize the tissue,” says Marcu. “Surgeons can determine in real time whether they have healthy margins. It would save time, money and be better for patients.”
Marcu’s team is currently working in the lab on tissue specimens, but the technology is ready to be used in patients.
The all-important sentinel node biopsy
For decades the trend has been to reduce the amount of tissue taken out during breast cancer surgery. Radical mastectomy, which removes the entire breast and some of the underlying muscle, made way for lumpectomies.
Unfortunately, the desire to minimize surgery runs up against a hard reality: cancer spreads. For a lumpectomy to succeed, clinicians must make sure tumor cells have not infiltrated the lymphatic system. In the past, cancer surgeons removed all the lymph nodes in an area under the shoulder called the axilla. But this led to severe side effects, such as painful swelling in the arm from fluid buildup.
The better solution has been to find the node most likely to contain cancer cells — the sentinel node. Currently, surgeons inject a radioactive solution near the tumor and use a small Geiger counter to track where it goes. But UC Davis researchers are working on a better way to find the sentinel node using a metal solution and magnetism instead of radiation.
“We’re trying to move away from unnecessary radiation exposure,” says Richard Bold, chief of surgical oncology and lead researcher on the project. “The radiation is low — we don’t think it’s a health risk — but if we can eliminate it, we should.”
But the new approach, called Sentimag, has another advantage: less discomfort for patients. Radioactive injections must be given an hour before surgery and are notoriously painful. The magnetic tracer used for Sentimag identification, however, is given during surgery when the patient is under anesthesia.
Mary Willian, who was diagnosed with invasive breast cancer, is an early advocate. As part of a clinical trial to validate Sentimag she experienced both methods.
“When they injected the radioactive liquid, that hurt,” says Willian. “But with the magnetic stuff, I didn’t even know they did it.”
Willian’s procedure produced only good news — the cancer had not spread. For Bold, the added rewards come in the days following surgery.
“Patients walk in a week after lumpectomy and lymph node biopsy and tell me they just went shopping. That’s the kind of recovery we like to see.”