The following article features coverage from the 2019 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The detection of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) after neoadjuvant therapy and surgery was associated with worse outcomes among patients with triple-negative breast cancer (TNBC), according to data from the phase 2 BRE12-158 trial. The data were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas.

The BRE12-158 trial enrolled 196 patients with TNBC who had significant residual disease after neoadjuvant chemotherapy followed by surgery. Patients were randomly assigned to receive either a genomically directed monotherapy or physician’s choice of therapy. After treatment randomization, plasma samples were collected for ctDNA detection and blood samples for CTC detection. 

The FoundationOne Liquid assay was used to evaluate ctDNA samples, and CTC positivity was defined as the presence of 1 or more CTC. 

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Patients with detectable ctDNA had a significantly worse distant disease-free survival (DDFS; hazard ratio [HR], 2.99; 95% CI, 1.38-6.48; P=.0055), disease-free survival (DFS; HR, 2.67; 95% CI, 1.28-5.57; P=.0069), and even overall survival (OS; HR, 4.16; 95% CI, 1.66-10.42; P=.0024) compared with patients without detectable ctDNA.


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The quantitative burden of ctDNA was also associated with significantly worse DDFS (HR, 4.83; 95% CI, 1.07-21.82; P=.041) and DFS (HR, 5.58; 95% CI, 1.35-23.05; P =.017) and showed a trend toward worse OS, but the result was not significant (HR, 4.55; 95% CI, 0.95-21.73; P=.058).

Although the mere detection of CTCs was not significantly associated with worse outcomes, if the CTC count was increasing, a significant association with DDFS (HR, 1.08; 95% CI, 1.03-1.14; P=.0026), DFS (HR, 1.10; 95% CI, 1.04-1.16; P=.00066), and OS (HR, 1.11; 95% CI, 1.04-1.19; P=.0019) was seen.

“Patients with TNBC at high clinical risk of relapse due to an incomplete response to neoadjuvant chemotherapy can be further risk-stratified based on the presence of MRD [minimal residual disease], as determined by ctDNA,” said the study presenter Milan Radovich, PhD, from the Indiana University School of Medicine in Indianapolis.

The analysis also showed that patients with both detectable ctDNA and CTCs had an even worse DDFS (HR, 5.29; 95% CI, 1.50-18.62; P=.0095), DFS (HR, 3.15; 95% CI, 1.07-9.27; Pv=.037), and OS (HR, 8.60; 95% CI, 1.78-41.47; P=.0074). 

“The addition of CTCs adds complementary information to ctDNA for detection of MRD,” Dr Radovich added. 

The study authors are planning to continue studying ctDNA in patients with TNBC by launching the BRE18-334 trial, which will also be known as the PERSEVERE trial.

Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of SABCS by visiting the conference page.

Reference

  1. Radovich M, Jiang G, Chitambar C, et al. Detection of circulating tumor DNA (ctDNA) after neoadjuvant chemotherapy is significantly associated with disease recurrence in early-stage triple-negative breast cancer (TNBC): Preplanned correlative results from clinical trial BRE12-158. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-02.