Posted: Tuesday, May 17, 2022
Clare M. Isacke, PhD, of The Institute of Cancer Research, London, and colleagues used ultra–low-pass whole-genome sequencing to detect circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) of patients with breast cancer leptomeningeal metastasis. Published in Clinical Cancer Research, their results concluded that this type of sequencing demonstrates potential for accurate and timely diagnosis and therapy response monitoring, with future aims to improve disease management.
“Leptomeningeal metastasis is an aggressive type of advanced breast cancer that has an average survival rate of just 3 to 4 months and urgently needs more research,” stated Dr. Isacke in an institutional press release. “This test shows real promise..., as it will allow doctors to predict, and more accurately measure, how well a patient will respond to therapy.”
Cell-free DNA was extracted from the CSF and plasma of 30 patients undergoing investigation for breast cancer leptomeningeal metastasis. Ultra–low-pass whole-genome sequencing was used to assess ctDNA fraction.
A total of 24 patients were found to be positive for breast cancer leptomeningeal metastasis, with ctDNA detected in the CSF of all patients; CSF ctDNA was not detected in patients who tested negative for metastasis (P < .0001). Of note, plasma ctDNA was primarily detected in participants who previously underwent whole-brain radiotherapy or experienced extracranial disease progression.
In addition, the ctDNA fraction was highly associated with mutant allele fraction, which was measured by tumor mutation–specific droplet digital polymerase chain reaction assays (P < .0001). Furthermore, serial monitoring (n = 12) showed that when the CSF ctDNA fraction was suppressed during intrathecal treatment, it appeared to be associated with longer survival with breast cancer leptomeningeal metastasis (P = .034); the rising ctDNA fraction seemed to be detectable for up to 12 weeks before disease progression.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.