In Breast Cancer, a Blood Test Could Determine the Next Stage of Therapy

Researchers in the United Kingdom have identified a blood test for circulating free DNA that may help physicians predict whether or not a patient with breast cancer is likely to respond to an initial round of chemotherapy, enabling earlier initiation of alternate treatments.

In patients with metastatic breast cancer, a new test of circulating free DNA, or cfDNA, may help physicians predict the likelihood of relapse for individual patients who have received an initial treatment course.

Dr Nicholas C. Turner, MD, PhD, and colleagues at the Institute of Cancer Research Division of Breast Cancer Research, studied 20 patients who received chemotherapy to reduce the size of breast cancer tumors before surgery.

Scientists drew samples of blood plasma from each patient to measure cfDNA. Extraction of samples occurred before chemotherapy, after surgery, and every 6 months thereafter.

Using targeted sequencing technology, the scientists assessed tumors for presence of mutations and checked these mutations against mutations in cfDNA drawn from blood. In more than half (60%) of patients, tumors were found to contain at least 1 mutation. Mutations found directly in tumor samples correlated well with the mutations found in cfDNA, with an r-squared value of 95% for the correlation.

Investigators identified detectable mutations in the cfDNA of 4 of the 20 patients involved in the study within 6 months of breast cancer surgery. All 4 of these patients experienced a relapse of breast cancer. The remaining 16 patients did not have detectable mutations in cfDNA samples, indicating a favorable response to treatment.

Even with a very small sample of patients, investigators found that the 4 instances of relapse versus 12 instances of complete response represented a significant predictive effect for cfDNA levels on the likelihood of experiencing a relapse of breast cancer (P = .01).

These results show that tumor-specific mutation tracking using a test of peripheral blood can predict whether or not patients are likely to respond to treatment. This kind of testing may enable patients who are not doing well on initial therapy to attempt treatment with novel agents, while protecting patients who have already experienced a good response to initial treatment from the potential hazards of novel agents.

Although more research is required, these initial results may be the start of a new standard of care in the treatment of breast cancer. For instance, it would not be difficult to imagine a treatment algorithm in which a cfDNA blood test would determine the next stage of treatment after an initial therapeutic regimen for breast cancer.

A well-validated test would offer patients assurance for the durability of a positive initial outcome after treatment, and would offer patients who are not experiencing a good response to initiate another mode of treatment before another breast cancer relapse begins.

Reference:

• Turner NC, Garcia-Murillas I, Schiavon G, et al. Tracking tumor-specific mutations in circulating-free DNA to predict early relapse after treatment of primary breast cancer. J Clin Oncol. 2014;32:5(suppl): Abstract 511.