Hope for alternatives to painful biopsies

A blood test to detect cancer mutations produced results that generally agree with those of an invasive tumor biopsy, researchers reported, heralding a time when diagnosing cancer and monitoring its progression may become less painful and risky. The blood tests, known as liquid biopsies, represent one of the hottest trends in oncology. They take advantage of the fact that DNA fragments from tumours can be found in tiny amounts in the blood of patients with cancer.

Researchers hope that such tests can become alternatives to conventional tumour biopsies, in which a piece of the tumour is extracted by needle or by surgery — procedures that can have complications. The results of the study, the largest to date of a liquid biopsy test, give some reassurance that this might be possible. “I think this study really demonstrates the veracity of the liquid biopsy approach,” said Dr Philip Mack, director of molecular pharmacology at the University of California Davis Comprehensive Cancer Center.

The liquid biopsies are not used to diagnose cancer but rather to monitor disease progression or to detect genetic mutations in the tumour that could suggest which drug should be used to treat the disease. Just this week, the US Food and Drug Administration gave its first approval for such a test, one developed by Roche (pharmaceutical firm) to detect mutations in a particular gene.

Lung cancers with mutations in that gene are vulnerable to treatment with certain drugs, including Roche’s own Tarceva. Many liquid biopsy tests are being sold by other companies under rules that do not require FDA approval.

The study looked at the results of more than 15,000 liquid biopsies performed by Guardant Health, a Silicon Valley startup that is one of the leaders in the field. While many liquid biopsy tests now look for only a few mutations, Guardant’s test, which has a list price of $5,800, looks at mutations in 70 cancer-related genes.

The 15,000 samples came from the blood of people with various types of cancer, including lung, breast and colorectal. The researchers on the study, most of whom worked for Guardant, said the frequency and types of mutations found were similar to what is known from scientific literature.

For almost 400 patients, tumour biopsies were available, allowing for direct comparison to the blood test results from the same patient. For certain mutations that drive tumour growth, if a particular mutation was found in the blood, it was also found in the tumour 94-100% of the time.

There was much less agreement for mutations that predict resistance to particular drugs. Those might have arisen only after the treatment started, so might not have been seen in the tumour biopsy, which is usually taken at the time of diagnosis.

One shortcoming of the liquid biopsy was that for about 15% of the patients overall, no tumour DNA was detected in the blood. “There are simply tumours that do not shed DNA into circulation at detectable levels, so we are bound to miss them,” said Mack, who has been a paid speaker for Guardant.

Dr Edward Kim, an expert on lung cancer mutations who was not involved in the study, said the results showed the liquid biopsy accuracy was “very good.” He said, however, that use of an actual tumour sample allows for a more thorough analysis, including more mutations than is possible with a blood sample.

“I’m not personally ready to give up tissue,” said Dr Edward, who is the chairman of solid tumour oncology at the Carolinas HealthCare System’s Levine Cancer Institute in Charlotte, North Carolina. “It’s still the gold standard.” Still, he said, there are times when a tissue biopsy cannot be obtained, and it is difficult to do second and third tissue biopsies on a patient. In those cases, he said, “I love the option of having the blood test available.”