Circulating tumor DNA (ctDNA) may serve as a prognostic surrogate for overall survival in patients with metastatic breast cancer, independent of disease burden, according to research presented at the 2024 San Antonio Breast Cancer Symposium.

Although ctDNA is regularly used for tumor genotyping and mutation detection in metastatic breast cancer, its value as a prognostic indicator remains unestablished. Researchers from Memorial Sloan Kettering Cancer Center created a cohort using ctDNA assessments from MSK-ACCESS, an assay of 129 cancer-related genes.

A total of 685 patients with metastatic breast cancer had at least one MSK-ACCESS assessment and complete clinical information available. The death rate for patients at data lock was 42%. The researchers observed detectable ctDNA in 73% of patients, with a median maximum variant allele frequency of 2.4% (interquartile range, 0.53-12.7).

The presence of ctDNA was associated strongly with the number of metastatic sites (≥ 3, 2.9%; 2, 1.6%; 1, 0.7%; P = .00047) and the presence of liver metastases (1.5% vs 0.76%; P = .0013). Compared with triple-negative breast cancer and HER2-positive breast cancer, ctDNA levels were lower in ctDNA-positive patients with HR-positive, HER2-negative breast cancer (4.2% vs 4.6% vs 1.9%; P = .031).

The presence of ctDNA served as a strong prognostic variable for overall survival in univariate (hazard ratio [HR] = 3.9; 95% CI, 2.7-5.8) and multivariate (HR = 3.7; 95% CI, 2.5-5.4) analyses. The level of ctDNA was also prognostic (< 1%, HR = 2.2; 1%-10%, HR = 3.9; ≥ 10%, HR = 7.3). The number of mutations was also associated with overall survival (1-2, HR = 2.8; ≥ 2, HR = 5.8).

In an analysis of receptor type, ctDNA served as a prognostic factor for patients with HR-positive/HER2-negative and triple-negative breast cancer (P = .00045), but not for patients with HER2-positive breast cancer.

“ctDNA level remained an independent prognostic factor for OS in a multivariable analysis adjusted for visceral metastasis, number of metastatic sites (at the time of metastatic relapse), and receptor subtype (HR = 6.7; 95% CI, 4.4-10.2). Similar results were obtained using median, mean, and geometric mean variant allele frequency to estimate ctDNA levels.”

-Luc Cabel, MD, PhD, visiting investigator at Memorial Sloan Kettering Cancer Center, and colleagues

ctDNA levels remained an independent prognosticator for OS after adjustment in an analysis restricted to 152 patients with ctDNA samples obtained within 3 months of metastatic diagnosis (HR = 4.5; 95% CI, 1.5-13).

“Our data suggest that ctDNA levels can provide valuable insight into tumor biology as well as disease burden and may be utilized for early prognostication in metastatic breast cancer.”

-Cabel and colleagues

Reference:
https://sabcs.org/Portals/0/Documents/Formatted_Abstracts%2011-27%20Without%20Embargoed.pdf?ver=qjVzk5LPNjOteEIvNEYJFw%3d%3d

Disclosures: MD /alert could not confirm financial disclosures at the time of reporting.

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