Spokane-based Rockwood Clinic PS is participating in a clinical study of a technique to identify genetic markers in cancerous breast tumors that can help doctors predict whether a cancer patient is at risk for developing metastatic cancer later.

Already, Rockwood specialists have altered two patients' treatment plans because of results from the test, called MammaPrint, and Dr. Renu Sinha, the principal investigator in the study here, hopes the technique will improve breast-cancer treatment outcomes for patients.

The study, which will help evaluate the test's effectiveness further, will kick into high gear here in April, Sinha says.

The technology was designed by Agendia, a company based in Amsterdam, the Netherlands, that calls itself "a world leader in molecular cancer diagnostics." The test was approved for use in the U.S. by the Food and Drug Administration in 2007, but is not widely in use here yet.

MammaPrint provides information about a tumor sample by testing for 70 genetic markers, allowing cancer specialists to individualize treatment protocols for women diagnosed with breast cancer, Sinha says. It predicts with 97 percent accuracy which women are at high risk of developing metastatic cancer in the next 10 years.

Metastatic cancer is the spread of a cancer from its original site to other places in the body, and the genetic markers examined by the MammaPrint genetic test identify cancers that are more likely to spread.

When a woman is found to be at high risk for a metastatic breast cancer recurrence, a multidisciplinary treatment team often recommends aggressive treatments, such as chemotherapy, to kill any possible dormant metastatic cells.

The current methods for gauging such risk are based mostly on factors such as age and family history and are compared with collective historical data from other patients, which, while useful, are less precise than use of the MammaPrint, Sinha says.

One of Sinha's goals is to reduce the cost of treating breast cancer by gauging risk more precisely. A woman determined to be at relatively low risk for developing metastatic cancer could be spared the physical risk and expense of undergoing aggressive therapies, Sinha says. She says the cost of chemotherapy and other cancer treatments can range anywhere from tens of thousands of dollars to hundreds of thousands of dollars.

Undergoing chemotherapy, radiation therapy, or surgery also entails a lot of personal and lifestyle costs, such as time lost from work, loss of family interaction, and emotional stress, Sinha says.

"If we can target treatment, we can decrease the cost," she says.

Emerging technology

MammaPrint has been used in European countries for about five years, but is not well-known here yet, although it's the only FDA-approved genetic test for breast-cancer validation, Sinha says.

A physician collects a sample of about 30 percent of the total mass of a tumor, either through a needle biopsy procedure in the doctor's office or surgically, and puts the tissue sample into a vial that contains a patented solution called RNARetain solution.

RNARetain stabilizes the genetic material in the sample so the sample can be shipped at room temperature, ensuring that the tissue arrives intact and is less likely to be degraded by fluctuations in temperature. Other similar tests require samples to be shipped frozen, creating more risk that a sample could be damaged in transit, Sinha says.

Once the sample is suspended in the solution, it is shipped via FedEx to Agendia's lab in Amsterdam for testing, and results are returned to the clinic within 10 days, Sinha says. That turnaround time likely will be reduced, however, when Agendia opens a lab next month in Huntington Beach, Calif., she says.

The results then are reviewed by Rockwood Clinic's multidisciplinary tumor board, and an individualized treatment protocol is developed for the patient.

There are some other similar tests, which like the MammaPrint are referred to as genetic expression tests, available in the U.S., but none that is FDA approved, Sinha says. One such test is produced by Genomic Health Inc., of Redwood City, Calif. Sinha says that test, called the Oncotype DX, is somewhat more limited than the MammaPrint in that tissue samples must be shipped frozen to the lab, and is only used to test tumors that are node-negative and estrogen-positive, meaning they are stimulated by estrogen to grow.

Another frequently-used risk assessment is called Adjuvant! Online, a database that uses data collected from women who have had cancer to predict an individual's risk of future disease and to calculate the benefit of chemotherapy and other treatments. Sinha says among patients whose data are entered into Adjuvant! Online, MammaPrint results so far have found that about 30 percent of patients predicted to be high risk based on data from that program actually are at low risk of future metastatic disease based on the genetic makeup of their tumor.

Rockwood will study 50 patients

Rockwood is one of 10 research sites in the world participating in the MammaPrint study, and the only one in the Pacific Northwest. Sinha says the center here hopes to include 50 patients in the study over the next several years.

To be included, patients must be under the age of 61 and must have a tumor that is less than 5 centimeters in diameter.

During the study, Rockwood Clinic will collect data that will help determine MammaPrint's effectiveness at predicting risk in various ethnic populations, will compare further its effectiveness to conventional diagnostic tools, and will collect data on how use of the test changes clinical therapy and outcomes.

Agendia is paying for the study and the testing, which costs about $3,000 per patient, Sinha says. Rockwood Clinic will be supporting the study with its research department here.

The two study participants already enrolled here were at opposite ends of the risk spectrum and both had their treatment plans altered radically because of the MammaPrint results, Sinha says.

One of those patients was an older woman with a small tumor. Using a computer-based risk model, the woman was identified as having a low risk for recurrence, but the MammaPrint genetic test indicated that she was at high risk for metastatic disease.

"That really changed our therapy for the patient," Sinha says.

Another patient was 40 years old and would have been recommended for chemotherapy because of her age and the size of the tumor, but the MammaPrint results indicated she would be at low risk for future metastatic disease, Sinha says.

"We decided it would be optional for her to do chemo," Sinha says. "She was tickled pink," because she had an active lifestyle and young children that she feared would be affected if she underwent chemotherapy.

Sinha says she expects the test results to confirm and refine the information from other risk models, but they could differ in 20 percent to 30 percent of the cases, she says.

Sinha says that the other tests will remain relevant, helping to create a total picture for clinicians treating breast cancer. She hopes that the MammaPrint data ultimately will help doctors personalize cancer treatment better so women who don't need chemotherapy won't have to endure it.

It's an advance that also has great future potential for further research to refine and personalize treatment methods for breast cancer, Sinha says.

"If you know the genetic defects that cause breast cancer, you can develop immunotherapy or target which chemotherapy can shut this particular defect down," she says.