Finding mutations, matching treatments

Clinical trial indicates that blood test beats biopsies for breast cancer

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LONDON—Breast cancer, the most common cancer in the United Kingdom, shows up in 55,200 new cases per year. Women diagnosed later or relapsing after treatment have limited treatment options, and if the cancer is diagnosed at the latest stage, only one in four people (25 percent) will survive the disease for five years or more.
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Some breast cancers with specific mutations, or genetic defects, can be targeted directly with new drugs undergoing testing in clinical trials. Since these defects are rare, it is critical to determine which patients could benefit most. Currently, these defects are identified by taking out a piece of the tumor via biopsy or during surgery, a slow, invasive process that may be inaccurate after treatment or when cancer spreads.
Cancer Research UK scientists have found that a blood test can help identify rare mutations in advanced breast cancer, potentially enabling patients to access effective treatments more quickly in the future. Their results were presented at the 2019 San Antonio Breast Cancer Symposium.
As part of the plasmaMATCH clinical trial—funded by Stand Up To Cancer, a joint fundraising campaign from Cancer Research UK and a television station—the researchers were able to discover mutations in the DNA from the tumors, which shed cells into the bloodstream. Specific weaknesses in the breast cancer DNA could be targeted with drugs, suggesting that this blood test may be a better way to guide treatment than standard tissue biopsies that can be painful and take longer to analyze.
Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust analyzed the blood from around 1,000 women with breast cancer whose cancer had returned after treatment or had spread to another part of the body. The researchers wanted to determine whether taking a liquid biopsy, where traces of tumor DNA circulating in the blood could be detected, was a faster and easier alternative to traditional tumor testing.
The new study was designed to determine whether a blood test could detect three targetable defects in HER2, ESR1 and AKT1 genes, which are known to drive breast cancer. In the study, 142 women with these detectable mutations received experimental targeted therapies against the specific characteristics of their cancer. Treatments that have shown initial promise will be tested further in larger clinical trials. To validate their findings, the researchers also checked tissue samples from the patients and confirmed that the liquid biopsy had correctly identified the presence or absence of the mutations in over 95 percent of the cases. These findings suggest that the blood test could be a robust way to identify rare subtypes of breast cancer and could potentially replace the more invasive methods of analyzing breast tumors.
According to Nicholas Turner, professor of molecular oncology at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden, “The choice of targeted treatment we give to patients is usually based on the mutations found in the original breast tumor, but their cancer can have different mutations after it has moved to other parts of the body. We have now confirmed that blood tests can quickly give us a bigger picture of the mutations present within multiple tumors throughout the body, getting the results back to patients accurately and faster than we could before. This is a huge step in terms of making decisions in the clinic, particularly for those women with advanced breast cancer who could quickly be put on new targeted treatments matched to their cancer if it evolves to become drug-resistant.”
The researchers maintain that the blood tests are reliable enough to be used routinely by doctors once they have passed regulatory approval. For the targeted drugs still in development, the next step is to carry out larger clinical trials to determine whether they are better than existing treatments.
As Prof. Carlos Caldas, senior group leader at the Cancer Research UK Cambridge Institute, said, “This work builds on increasing evidence in favor of liquid biopsies. It’s another step in the right direction and could mean a lot to people with advanced breast cancer, because it can identify those who may benefit from new targeted treatment after other options have stopped working. Liquid biopsies are also showing promise beyond guiding treatment choices. It’s relatively easy to take a blood sample, which means the test could be used to monitor how cancer responds throughout a course of treatment, or it may be able to detect the early signs of treatment resistance.”

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