Liquid biopsy may predict early-stage TNBC recurrence
medwireNews: The presence of circulating tumor (ct)DNA and circulating tumor cells (CTCs) in postsurgical samples is associated with relapse and poor outcomes in early-stage triple-negative breast cancer (TNBC) patients with an incomplete pathologic response to neoadjuvant chemotherapy, research suggests.
Distant disease-free survival (DDFS), DFS, and overall survival (OS) were significantly worse for patients with versus without these tumor markers, say the investigators who conducted a prespecified secondary analysis of the phase 2 BRE12-158 trial.
The primary aim of the trial was to investigate the efficacy of adjuvant genomically directed therapy versus physician’s choice of treatment in TNBC patients who had residual disease after neoadjuvant therapy and surgery. The current analysis evaluated ctDNA and CTCs in postsurgical samples collected prior to initiation of targeted therapy or at the first routine visit depending on the randomization group.
As reported in JAMA Oncology, ctDNA was successfully sequenced for 142 of the 177 evaluable trial participants, while CTCs were detected for 123 participants.
Patients who were positive for ctDNA had significantly worse DDFS compared with their counterparts who were negative for ctDNA, at a median of 32.5 months versus unreached, and a hazard ratio (HR) of 2.99. The estimated 24-month DDFS rates were 56% and 81%, respectively.
DFS and OS were similarly poorer for ctDNA-positive than ctDNA-negative participants, with significant HRs of 2.67 and 4.16, respectively, and estimated 24-month DFS rates of 50% versus 76% and OS rates of 57% versus 80%.
Bryan Schneider (Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, USA) and colleagues highlight that “[a]lthough patients who were CTC positive had inferior outcomes, results did not reach statistical significance.”
However, the findings were statistically significant when increasing CTC counts were considered, “suggesting that the quantitative burden of CTCs is associated with outcomes,” they write.
Moreover, combining ctDNA and CTCs “provided additional information” about the likelihood of minimal residual disease, say Schneider and colleagues. Specifically, DDFS was significantly worse for patients who were positive for both markers versus those who were negative for both, with an HR of 5.29, and estimated 24-month rates of 52% versus 89%. And this was also the case for DFS and OS (HR=3.15 and 8.60, respectively).
“The strength of these findings, along with the prior body of literature, now supports the routine use of this technology for proper risk stratification across clinical trials in the curative setting,” conclude the researchers.
Writing in an accompanying editorial, Andrew Davis and Massimo Cristofanilli, both from Northwestern University in Chicago, Illinois, USA, agree that “the findings presented here and in other studies reinforce the importance of biological stratification in clinical trial design beyond standard clinical and pathologic variables.”
But they add: “Moving forward, we believe that the most important question for the field is to determine whether the detection of [minimal residual disease] and early treatment initiation based on this information improve[s] patient outcomes.”
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