Expanded DNA Testing Might Allow Personalized Breast Cancer Treatment

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Testing the entire genetic makeup — or all the DNA — of tumor cells from women with advanced breast cancer may help identify patients who could be helped by specific treatments, according to new research.

The approach is considered the wave of the future by both the French researchers who conducted the study and U.S. experts.

“It is possible to deliver personalized medicine,” said study researcher Dr. Fabrice Andre, of the Gustave Roussy Institute in Villejuif, France. “Until now, we could [test] one gene in a large number of patients, or larger numbers of genes in a few patients.”

In the new study, the researchers evaluated the whole genome — the entire collection of a person’s genes — of more than 400 patients. The approach is much more extensive than testing for mutations in specific genes, such as the BRCA1 and BRCA2 genetic mutations known to raise the risk of breast cancer.

From 2011 to 2012, Andre’s team evaluated the women from 18 centers in France, all of whom had breast cancer that had spread. First they took biopsy samples. Then they conducted the whole-genome analysis to see if they could find unique characteristics and abnormal genes that could then be targeted for treatment in clinical trials.

Nearly half of the patients were found to have a genetic alteration that could be addressed with targeted treatment. Another 39 percent of women had rare alterations, many of which don’t have treatments currently available, the researchers said.

Next, the researchers matched 55 of the women with new treatments being tested in clinical trials, targeting them to the women’s specific genetic alteration. Of those, 43 women received the targeted treatments. And of those, four women had a response and nine others had stable disease for more than 16 weeks, the researchers said.

The study findings were published online Feb. 7 in the journal The Lancet Oncology.

Some of the larger cancer centers in the United States are also working on the whole-genome approach, said Dr. George Somlo, a professor of medical oncology and therapeutics research at the City of Hope Comprehensive Cancer Center, in Duarte, Calif. He reviewed the findings but was not involved in the study.

“It is very expensive, very labor intensive,” he said. “In the United States, the approach is evolving.”

The cost of whole-genome testing varies greatly, but some laboratories offer it for less than $10,000. Experts say the cost will drop more in the future.

Dr. Claudine Isaacs, a professor of oncology at the Georgetown Lombardi Comprehensive Cancer Center, in Washington, D.C., said the approach has advantages.

“The advantage of screening the tumor either for a large battery of mutations or doing whole-genome analysis is that it gives a much broader analysis and understanding of possible patient- or tumor-specific molecular ‘drivers’ for that particular tumor,” said Isaacs, who also reviewed the findings. “It will pick up both suspected and unsuspected [genetic] alterations.”

“I do think this is the wave of the future,” she said. “The hope of such an approach is to better provide our patients with a personalized approach to their care.”

As promising as the approach is, Somlo said, it’s important to realize that “not every tumor needs to have whole-genome testing.” It’s already known that some specific mutations or changes in genetic activity will result in particular breast cancer patients benefiting from targeted therapy, he said.

For instance, he said, the drug trastuzumab (Herceptin) is used as a targeted therapy for women found to be over-activating the protein known as HER2 (human epidermal growth factor receptor).

For breast cancer patients, the difficulty of finding an effective treatment increases when the disease spreads, Somlo said.

“There are multiple mutations and the curability of those patients is very low,” he said. Obtaining the genetic information in these cases would best be done as soon as possible after the cancer’s spread is detected, he said.

More information

To learn more about human genomes, visit the U.S. National Institutes of Health.

Source: HealthDay

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