ctDNA Levels May Predict Treatment Response in Advanced Breast Cancer

Among patients with advanced breast cancer, levels of circulating tumor DNA, also known as ctDNA, prior to starting treatment, may predict their response to targeted therapy, researchers have determined.

The findings, which show that baseline low ctDNA levels may predict a response to targeted therapy, were detailed in a study findings of which were published in the journal Clinical Cancer Research.

ctDNA, as defined by the National Cancer Institute on its website, is the term used to describe small pieces of DNA that are released into a patient’s body by tumor cells as they die, and a sample of blood can be used to look for and measure the amount of ctDNA and identify specific mutations in the DNA.

Researchers assessed ctDNA levels at baseline and on-treatment dynamics among 167 patients with advanced breast cancer in the plasmaMATCH trial, and found that for some patients low baseline levels of ctDNA were associated with longer progression-free survival, or the time a patient lives without their disease spreading or worsening, and higher objective response rates.

The team behind the study grouped patients based on their type of breast cancer and the specific mutations in their genes, with the first group consisting of patients whose cancers had an ESR1, HER2, AKT1, AKT or PTEN mutation, and who received targeted treatments matched to those mutations and the second group consisting of people with triple negative breast cancer and no targetable mutation who received a combination of the PARP inhibitor Lynparza (olarparib) and the ATR inhibitor ceralasertib.

As explained in a news release issued by the Institute of Cancer Research, in patients in the second group, low levels of ctDNA prior to treatment were associated with progression-free survival of 10.2 months versus 4.4 months, and in this group 40% of patients with low ctDNA levels responded to treatment, versus 9.7% of patients with higher levels of ctDNA in their blood.

Furthermore, following four weeks of treatment patients in the first group with undetectable ctDNA had a median progression-free survival of 10.6 months versus 3.5 months for patients with detectable ctDNA. Among patients in this group, 46.2% of patients with low levels of ctDNA after four weeks responded to treatment, versus 7.9% of patients with high levels of ctDNA.

Additionally, for patients in the second group, after four weeks of treatment patients without detectable ctDNA had a median progression-free survival of 12 months versus 4.3 months for patients with detectable ctDNA, while 85.7% of patients with undetectable ctDNA responded to therapy versus 11.4% of patients with detectable ctDNA.

“By analyzing circulating tumor DNA in blood samples from patients with advanced breast cancer, we identified a clear link between these levels, both at the start and after one cycle of treatment, and how well patients responded to therapy,” Dr. Iseult Browne, clinical research fellow at The Institute of Cancer Research, London, and first author of the study, said in the news release. “Patients with low or undetectable ctDNA consistently had better outcomes, including longer progression-free survival and higher response rates. These findings support the use of ctDNA as a non-invasive biomarker for predicting outcomes and monitoring treatment response.”

“Our study shows that a simple blood test could give us an early and reliable indication of whether treatment is working for people with metastatic breast cancer,” Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, and study lead, said in the news release. “By tracking changes in tumor DNA in the blood just a few weeks into treatment, we can begin to identify who is likely to benefit and who may need a different approach sooner. This has the potential to make treatment decisions faster, more personalized and ultimately more effective for people living with metastatic breast cancer.”

References

1. The Prognostic and Predictive Impact of ctDNA Levels in Patients with Advanced Breast Cancer Enrolled on the plasmaMATCH Trial,” by Dr. Iseult M. Browne et al., Clinical Cancer Research.
2. “ctDNA,” National Cancer Institute; https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ctdna
3. “Breast cancer blood test can predict treatment response,” The Institute of Cancer Research; https://www.icr.ac.uk/about-us/icr-news/detail/breast-cancer-blood-test-can-predict-treatment-response

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