A negative plasma result is conditional on assay and collection window

For standardized ctDNA ESR1 testing, cross-platform agreement alone would not establish the meaning of a negative result. Interpretation should be indexed to the mutation panel, baseline tumor genotype, plasma volume and DNA input, allele-fraction detection limits, and timing relative to therapy. In a multicentre setting, false-negative behavior should also be reported by platform and testing site. Host-derived mutations add another reason to distinguish analytical detection from tumor attribution rather than treating all plasma variants as equivalent evidence.