Blood Test Detects New Breast Cancer Subtype

A blood test has been developed that detects when the most common form of breast cancer has become resistant to treatment could double the average time it takes for the disease to progress, from around two and a half to around six months.

The test detects mutations to a gene called estrogen receptor 1, or ESR1, which indicate that receptors for the female hormone estrogen in the cancer cells that are usually driven by the hormone have evolved to stay permanently switched on without it which means hormonal treatments that block estrogen production will no longer be effective.


Scientists at the Institute of Cancer Research (London, UK) and their colleagues analyzed blood samples from a total of 783 women enrolled on two major phase III clinical trials of new treatments for advanced estrogen receptor positive breast cancer, which accounts for three quarters of all cases. DNA extraction was performed using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Hilden, Germany).

Total free DNA was quantified from plasma using RNase P as the reference gene. For ESR1 mutation analysis, the team used commercially available multiplex droplet digital polymerase chain reaction (ddPCR) assays for the seven most common ESR1 mutations. The ddPCR was performed on a QX200 system (Bio-Rad, Hercules, CA, USA). A multiplex assay was considered mutation positive if at least two ESR1 mutant droplets were observed. The results obtained on the multiplex ddPCR were further characterized using uniplex ddPCR assays.

The investigators found that nearly 40% of the 162 patient blood samples available, taken going into the trial, were found to have mutations in the estrogen receptor. These women responded better to fulvestrant, which delayed progression of the disease for 5.7 months, compared to 2.6 months on exemestane. For women without ESR1 mutations both treatments, fulvestrant and exemestane, had the same effectiveness.

The scientists also looked at a second trial that had compared treatment with fulvestrant and a placebo to fulvestrant and palbociclib. They found 25.3 %of patient blood samples had estrogen receptor mutations going into this trial. But because palbociclib targets different molecules, the patients had the same outcomes regardless of whether or not they had the mutation in the estrogen receptor.

Nicholas Turner, MD, PhD, a medical oncologist and team leader said, “Our results show that breast cancer with and without ESR1 mutations are distinct subtypes that respond differently to treatment. These subtypes can be diagnosed simply and cheaply from a blood test, and should be considered for future clinical trials of advanced breast cancer to ensure patients are receiving the best treatment for their cancer. For the first time we should able to use a potentially simple test to help us pick the best treatment for women with advanced cancer after their initial treatment has failed. We do need to confirm the results in another trial before we can implement this clinically.” The study was published on September 1, 2016, in the Journal of Clinical Oncology.

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