Researchers at Severance Hospital have developed a whole genome sequencing (WGS) circulating tumor DNA (ctDNA) assay to diagnose breast cancer genes more easily through a blood test.

In recent times, targeted sequencing assays have gained prominence in diagnosing ctDNA – the tumor DNA present in the blood of cancer patients. 

However, these assays had limitations, targeting only about 200 of the total genes in the body and lacking accuracy in detecting gene structural variants, thereby diminishing their value. 

As a result, the research team, led by Professors Sohn Joo-hyuk, Kim Min-hwan, and Kim Gun-min from the Department of Oncology at Yonsei Cancer Center, developed a new WGS ctDNA assay to detect tumor DNA in the blood of breast cancer patients. 

GC Genome Research Center Director Cho Eun-hae also participated in the study. 

The team emphasized that their test method is simpler than traditional genetic testing, which involves examining the entire genome to identify cancer genes. 

Instead, their method applies the non-invasive prenatal genetic testing technique that analyzes the mother's blood to identify genes causing malformations in the fetus. 

To determine the clinical applicability of the test, the researchers studied 207 breast cancer patients. 

They used blood samples taken from patients before they began chemotherapy and compared the genetic DNA analysis of tumor tissue with ctDNA analysis. 

The findings showed that the genetic alterations identified by the two methods were similar, confirming the accuracy of the ctDNA assay. 

The team also developed an I-score to predict survival and treatment response in breast cancer patients based on this assay. 

Patients with high I-scores were found to have more gene structural variants and more aggressive cancers, increasing their chances of recurrence and progression. 

To evaluate the functionality of the I-score, the researchers analyzed blood samples from 465 patients with triple-negative breast cancer (TNBC) participating in the PEARLY trial – a multicenter, phase 3 study conducted by the Korean Cancer Study Group. 

The two-year recurrence-free survival rate for patients with a high I-score and incomplete response to chemotherapy was 55.9 percent, compared to 96.9 percent for patients with a low I-score and complete response to chemotherapy. 

These results suggest that the I-score can accurately predict the risk of recurrence in patients with TNBC. The team added that the ctDNA assay can also be used to diagnose breast cancer types and target genes for targeted anticancer drugs, identify principles of targeted anticancer drug resistance, and analyze homologous recombination deletions (HRDs) to identify ovarian cancer gene mutations. 

"Through this method, we can identify cancer gene mutations in breast cancer patients using only a blood test without invasive biopsy," Professor Sohn said. "We expect the I-Score to enable personalized chemotherapy planning not only for patients with TNBC, which is particularly difficult to treat, but also for other cancer types."

The study was published in the Journal of National Cancer Institute.