Dr Rao on the Prognostic Value of Post-Surgical ctDNA Status in Early TNBC

“ctDNA status at that 2-to-4–week post-surgery time point gave better prognostic information than pCR, so this was a significant predictor for distant relapse–free interval.”

Ruta D. Rao, MD, a professor in the Department of Internal Medicine in the Division of Hematology, Oncology and Cell Therapy, director of the Coleman Foundation Comprehensive Breast Cancer Clinic, and medical director of the RUSH University Cancer Center, discussed findings from a prospective substudy of the phase 2/3 PARTNER trial (NCT03150576) evaluating the prognostic value of post-surgical circulating tumor DNA (ctDNA) status regarding distant recurrence in patients with early triple-negative breast cancer (TNBC).

The central objective of the analysis was to compare the prognostic power of 2 tumor-informed minimal residual disease assays, including one based on whole exome sequencing (WES) and the other using whole genome sequencing (WGS), to assess how their prognostic performance measured against pathologic complete response (pCR) rate with control chemotherapy on the PARTNER trial (36.4%), chemotherapy plus olaparib (Lynparza) on the PARTNER trial (54.6%), or control therapy not on the PARTNER trial, Rao began. The investigators collected serial blood samples for ctDNA at multiple predefined time points: at baseline, twice during neoadjuvant chemotherapy, once after neoadjuvant chemotherapy but before surgery, at 2 to 4 weeks following surgery, and again at 3 and 12 months after surgery, she explained. Both assays were performed for every patient, allowing a direct comparison of their informativeness.

The results demonstrated that ctDNA positivity in the postsurgical setting was highly prognostic for distant recurrence in patients with early-stage TNBC, a finding that held true across both the WES and WGS platforms, Rao stated. Building on the established prognostic significance of pCR status for recurrence, the investigators then compared pCR directly against ctDNA status. Notably, ctDNA status assessed at the 2-to-4–week post-surgical time point provided superior prognostic information relative to pCR status, Rao emphasized, functioning specifically as a significant predictor of distant relapse–free interval.