Detection of specific alterations in ctDNA prognostic in metastatic breast cancer
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Key takeaways:
- Women with TP53 and ESR1 alterations had worse survival than those without those alterations.
- Outcomes appeared similar regardless of ctDNA collection method.
The detection of specific genomic alterations in circulating tumor DNA appeared linked to poorer outcomes among women with metastatic breast cancer, according to study results.
The findings suggest circulating tumor DNA (ctDNA) could be a prognostic biomarker in this setting, researchers concluded.
“[Although] prognostic biomarkers are not yet clinically actionable, the field is moving in this direction,” Kyle Dickinson, PhD, researcher and laboratory manager at McGill University, and colleagues wrote. “By identifying the associations between prognosis and ctDNA, ctDNA can subsequently be correlated with specific therapeutic decisions in the future. These findings may guide the design of future clinical trials and prospective studies that will ultimately benefit patients with metastatic breast cancer.”
Despite advances in treatment for metastatic breast cancer, there are challenges that with regard to decision-making.
Tissue biopsies provide a static picture of the disease. Liquid biopsy with the detection of ctDNA is minimally invasive and provides stronger insight into tumors.
Dickinson and colleagues conducted a systematic review and meta-analysis to examine potential associations between ctDNA and survival among women with metastatic breast cancer.
Researchers searched five databases — CINAHL, Cochrane Library, Embase, Medline and Web of Science — and identified 37 eligible studies that included 4,264 women (age range, 20 to 94 years) with metastatic breast cancer.
All studies reported baseline ctDNA data and also reported OS, PFS and DFS outcomes.
Associations between detection of specific genomic alterations in ctDNA and survival served as the primary study outcome. Secondary objectives included associations of study methodology with survival.
Results showed a statistically significant association between ctDNA detection and shorter OS (HR = 1.4; 95% CI, 1.22–1.58).
Subgroup analysis revealed statistically significant associations between survival and detection of alterations in TP53 (HR = 1.58; 95% CI, 1.34-1.81) or ESR1 (HR = 1.28; 95% CI, 0.96-1.6). Researchers observed no association between survival and PIK3CA alterations.
Analyses stratified by detection method showed ctDNA detection through next-generation sequencing (HR = 1.48; 95% CI, 1.22-1.74) and digital polymerase chain reaction (HR = 1.28; 95% CI, 1.05-1.5) both were associated with shorter survival.
Researchers acknowledged study limitations, including the exclusion of several relevant studies due to lack of key information such as sample sizes of survival analyses, HRs and confidence intervals. Also, no studies in the analysis included men.
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Dickinson K, et al. JAMA Netw Open. 2024;doi: 10.1001/jamanetworkopen.2024.31722.
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