Blood Test Indicates Breast Cancer Tumors Developed Resistance to Hormone Treatment

Scientists developed a highly sensitive blood test that indicates when breast cancers become resistant to standard hormone treatment. In addition, the test results can be used to guide further treatment. The test provides an early warning of resistance to aromatase inhibitors, which are used to treat women with estrogen receptor (ER)-positive breast cancer. The test was described in Science Translational Medicine (2015; doi:10.1126/scitranslmed.aac7551).

The test could detect mutations to the estrogen receptor gene ESR1, which conveys resistance to hormone treatment, specifically in women treated with aromatase inhibitors. Detecting mutations in this gene from cancer DNA in the bloodstream could allow doctors to rapidly identify which patients are no longer benefiting from treatment and switch to an alternative drug.

The research team, from The Institute of Cancer Research (ICR), London, and The Royal Marsden NHS Foundation Trust in the United Kingdome, initially collected blood samples from 171 women with ER-positive breast cancer, and validated their results in 3 independent groups of patients.

They found that ESR1 mutations could be detected via multiplexed digital PCR analysis, an ultrasensitive method that reads the genetic code in tiny amounts of DNA released by tumors. This method proved able to detect DNA errors as sensitively as tumor biopsies, with 97% matching between the 2 methods and could, in the future, remove the need for an invasive biopsy procedure.

The researchers found that once ESR1 mutations were detected, mutated cancer cells multiplied and became the dominant type in the body, which drives the disease to become more aggressive and progress rapidly. Women who had breast cancers with ESR1 mutations were 3 times more likely to progress than those without.

The stage at which the cancer was treated had a huge influence over how cancers became resistant to aromatase inhibitors, a standard postsurgical treatment in postmenopausal women with ER-positive breast cancer. Mutations in ESR1 only occurred in 6% of patients first treated with aromatase inhibitors when their cancers had not spread; however, ESR1 mutations were in 36% of patients whose disease had already metastasized by the time the drugs were administered. The research suggests more advanced cancers evolve drug resistance much more readily, reinforcing the importance of early diagnosis and early treatment for cancer.

"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,” said study leader Nicholas Turner, MD, PhD, team leader in Molecular Oncology at ICR, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust.

"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 work was funded by several organizations including the NIHR Biomedical Research Centre at The Royal Marsden and ICR, Breast Cancer Now, The Cridlan Ross Smith Charitable Trust, and Cancer Research UK.

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