Oncology Central

Blood test provides early warning of resistance to aromatase inhibitors

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A blood test that is able to detect mutations in the estrogen receptor (ER) gene ESR1 in circulating cancer DNA and thus provide early warning of resistance to aromatase inhibitors has been developed by investigators at The Institute of Cancer Research (London,UK). Details of the test, which could assist clinicians in appropriately tailoring therapy to patients, appeared recently in Science Translational Medicine.

The initial investigation was carried out using blood samples from 171 women with ER-positive breast cancer and the results were then validated in three independent cohorts. Overall, it was determined that multiplexed digital PCR analysis could be employed to detect ESR1 mutations in the small amount of tumor DNA present in the samples.

The blood test was able to detect DNA errors sensitively when compared with results from conventional tumor biopsies, with 97% matching between the two procedures.

Nicholas Turner, study lead of The Institute of Cancer Research, explained: “Looking for cancer DNA in the blood allows us to analyze the genetic changes in cancer cells without the need for invasive biopsies. Our study demonstrates how these so-called liquid biopsies can be used to track the progress of treatment in the most common type of breast cancer. The test could give doctors an early warning of treatment failure and, as clinical trials of drugs that target ESR1 mutations are developed, help select the most appropriate treatment for women with advanced cancer.”

The team also discovered that once breast cancer cells develop ESR1 mutations, they become the dominant cancer cell type, rendering the disease more aggressive and accelerating progression. Women who had ER-positive breast cancers with ESR1 mutations were three times more likely to progress than those lacking the mutations.

The team also noted an association between the stage at which the cancer is treated and development of resistance to aromatase inhibitors. Among individuals first treated with this hormone therapy when their disease was still in a local stage, only 6% developed ESR1 mutations, compared with 36% in those first treated when the disease had spread. This would suggest that more advanced cancers evolve drug resistance much more readily, reinforcing the importance of early diagnosis and early treatment for cancer.

Source: The Institute of Cancer Research press release

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