314P - Concordance of somatic variants between circulating tumor DNA and tissue in patients with breast cancer

Background

Analysis of circulating tumor DNA (ctDNA) is a noninvasive method for detecting somatic variants. However, the sensitivity of ctDNA is limited by the dilution of ctDNA with cell-free DNA from non-cancer cells. In this study, we evaluated the concordance of somatic variants between ctDNA and tissue in patients with breast cancer to assess the clinical usefulness of ctDNA testing.

Methods

Paired plasma and tissue samples at the diagnosis were collected from 29 patients with breast cancer. Next-generation sequencing targeting 49 genes was performed on both plasma and tissue samples and the concordance between plasma and tissue was evaluated.

Results

A total of 140 variants were detected in paired tissue and plasma samples of 29 patients. Among them, 66.4% (93/140) of variants were detected only in tissue, 14.3% (20/140) of variants were detected only in plasma, and 19.3% (27/140) of variants were detected in both samples. The median variant allele frequency of concordant and discordant variants in ctDNA was 1.5% and 0.6%, respectively. Actionable variants were detected in four genes: BRCA1, BRCA2, ERBB2, and PIK3CA. For 29 patients, the overall concordance rate for detecting actionable variants was 65.5% (19/29), with individual gene concordance rates of 96.6% (28/29) for BRCA1, 93.1% (27/29) for BRCA2, 79.3% (23/29) for ERBB2, and 79.3% (23/29) for PIK3CA. The overall sensitivity and specificity were 41.2% and 100%, respectively.

Conclusions

ctDNA testing showed a high concordance and specificity in detecting actionable variants. It can be used as a complementary test to tissue biopsy for selecting appropriate therapeutic agents.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.