If circulating tumor DNA (ctDNA) can be detected in an adjuvant setting after both surgery and chemotherapy for early-stage breast cancer, patients are at high risk of early relapse, according to a proof-of-principle study. Researchers with the Institute of Cancer Research in London presented their results of their longer follow-up series on Wednesday, December 7, during the San Antonio Breast Cancer Symposium.

The researchers recruited a cohort of 43 women presenting with early-stage, primary breast cancer who were scheduled to receive neoadjuvant chemotherapy and in whom at least one somatic mutation was identified. Mutations were tracked with digital PCR to identify ctDNA in plasma samples taken either at a single post-surgical time point (two to six weeks post-surgery) or with serial plasma samples taken every six months in the adjuvant setting.

With a median 31.7 months of follow-up, 18 patients (42%) had relapsed. 

Detecting ctDNA at the single post-surgical time point was associated with both poor disease free survival (DFS) and overall survival (OS); all seven of the patients with ctDNA at the single post-surgical time point relapsed and died in the follow-up period, although the single post-surgery time point had modest 39% sensitivity for relapse. Poor DFS and OS also were associated with detection of ctDNA at any point in the serial sampling. All of the patients with detectable ctDNA relapsed in the follow-up period, showing a high specificity. ctDNA showed a 78% sensitivity for relapse, but the researchers added sensitivity was limited by three cases of brain-only relapse and one of solitary ovarian relapse. In the serial sampling, ctDNA detection had a median lead-time of 8.1 months over clinical relapse. 

The researchers added that the findings are not definitive, because “therapeutic trials are required to determine whether mutation tracking identifies relapse sufficiently early to allow for further adjuvant therapy.”