A novel blood test that measures genetic changes in circulating cancer DNA could help identify patients with metastatic breast cancer who could benefit from a change of treatment, new research has found.

Researchers funded by Cancer Research UK and Breast Cancer Now at the University of Leicester and Imperial College London demonstrated that a single blood test could detect and track alterations in 13 different genes, including some of the most important drivers of breast cancer such as the ERBB2 gene (HER2).

The test – one of a number of ‘liquid biopsies’ in development – can identify acquired changes to HER2 in patients with secondary breast cancer, indicating that HER2–targeted therapy, such as Herceptin, could be offered.

The test also detects mutations in the ESR1 gene, which has been linked to resistance to anti–hormone therapies such as aromatase inhibitors. Patients with this mutation could be eligible for a change of treatment to chemotherapy or other selective oestrogen receptor therapies such as fulvestrant (Faslodex).

This is the first time researchers have been able to analyse two types of acquired DNA mutation – called point mutations and copy number alterations (CNAs) – in a single blood test. However, further validation is needed to confirm its usefulness before any such test can be rolled out into the clinic.

Point mutations, which occur when the molecules that make up DNA are put together in the wrong order, can change the structure and function of the resulting protein. CNAs occur when extra copies of genes are incorporated into the DNA, and can lead to increased amounts of a particular protein. These types of mutation are both important drivers of breast cancer, and can affect how the disease responds to treatment.

In the study, published in the journal Clinical Chemistry, the researchers – led by Dr David Guttery and Professor Jacqui Shaw at the University of Leicester – first tested the approach using cell–line models in the lab, showing that the test accurately detected all of the expected changes in the cancer DNA.

Researchers then analysed DNA in blood samples donated by 42 women with secondary breast cancer, and detected cancer–specific genetic changes in half of these women. None of these mutations were found in an additional nine healthy women tested, which confirmed that the changes were due to cancer.

The results also supported previous findings that the amount of DNA can be used to track the progression of cancer – when cancer was growing more, there were increased levels of tumour DNA in the blood.

With genetic changes detected in 50% of the women, the researchers found that in nine of the 42 women – equivalent to roughly 1 in 5 patients – information from their secondary tumour DNA could have been used to alter their treatment.

The test identified that seven of the women whose cancers were progressing had increased copies of the HER2–coding gene. Of these seven, three had been HER2–negative at their first diagnosis – and that their secondary tumours had become HER2–positive indicates that they would have been eligible for Herceptin.

In addition, six of the women with hormone–driven cancers had mutations in the ESR1 gene, which has been linked to resistance to anti–hormone treatments. The best course of treatment for patients with this mutation is still under discussion, however in future, these women could be advised to stop anti–hormone therapy in favour of chemotherapy.