Circulating tumor DNA testing may inform next-line therapies in metastatic breast cancer
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Heterogeneity of serial circulating tumor DNA appeared associated with progressive disease among patients with metastatic breast cancer, according to study findings presented during the ASCO20 Virtual Scientific Program.
Researchers noted that assessment serial circulating tumor DNA (ctDNA) may enable detection of tumor genomic evolution and resistance mutations.
“ctDNA in progressive metastatic breast cancer can be used to discover progression and potentially identify mechanisms of resistance that can inform next-line therapies,” Saya Jacob, MD, of Northwestern University, told Healio.
Researchers at Northwestern collected ctDNA of 255 patients with metastatic breast cancer and used the Guardant360 (Guardant Health) assay to analyze samples. Eighty-six patients had a minimum of two serial ctDNA collections, with the second drawn at first progression by imaging and clinical assessment. Participants were no longer followed after second clinical progression.
Researchers analyzed type and number of alterations and mutant allele frequency, as well as sites of disease on imaging in close proximity to ctDNA evaluation.
Paired analysis indicated a rising number of alterations from baseline to PD-1 and PD-2, showing a heterogeneity of ctDNA associated with progressive disease. The most common mutations detected across all time points were TP53 and PIK3CA, with TP53 showing the highest increase in number of alterations at all time points. Data revealed mutant allele frequency and the number of genomic alterations increased simultaneously at time of progression.
According to Jacob, additional benefits of using ctDNA include the ease of collecting peripheral blood vs. tissue samples and the wide grasp of mutation detection. She emphasized the importance of learning cohorts in individual subtypes to determine the types of resistance mutations observed. Once clearer patterns are outlined, the next step would be drug development or targeted treatments, Jacob said.
Although the study showed a significant association of ctDNA heterogeneity with progressive disease, more research is needed to expand the function of precision medicine in metastatic breast cancer and use of targeted treatment based on ctDNA detection of resistance mutations, according to Jacob.
“It’s important in progressive cases where patients have already undergone several lines of therapy to really to determine the next best treatment that will minimize toxicity,” Jacob told Healio. “ctDNA is allows you to sample the tumor genetics over time and see how the tumor genetics are changing, and therefore how you must change your therapy.”
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