Blood Test Detects Resistance to Aromatase Inhibitors in Breast Cancer Treatment
Scientists have developed a highly sensitive blood test that can spot when breast cancers become resistant to standard hormone treatment, and have demonstrated that this test could guide further treatment. The test gives an early warning of resistance to aromatase inhibitors, which are used to treat women with estrogen receptor–positive breast cancer.
A team at The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust found that the test can 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 them to an alternative drug.
The work was published by Schiavon et al in Science Translational Medicine.
Study Details
Researchers initially took blood samples from 171 women with estrogen receptor–positive breast cancer and then validated their results in three independent groups of patients.
They found that ESR1 mutations could be detected by an ultrasensitive method known as multiplexed digital PCR analysis, which can read the genetic code of 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 two methods, and could in future remove the need for such an invasive procedure.
Researchers at the ICR and The Royal Marsden found that once ESR1 mutations were detected, mutated cancer cells multiplied and became the dominant type in the body, driving the disease to become more aggressive and progress rapidly. Women who had breast cancers with ESR1 mutations were three 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, which are used as standard therapy after surgery in postmenopausal women with estrogen receptor–positive breast cancer. Mutations in ESR1 only occurred in 6% of patients first treated with aromatase inhibitors when their cancers had not spread, but in 36% of patients when the 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.
Nicholas Turner, MD, PhD, Team Leader in Molecular Oncology at ICR and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said, “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 content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
