A negative liquid biopsy (ctDNA) result for HER2 amplification does not prove a patient is HER2-negative. The test's sensitivity is limited by tumor fraction in the blood. While a positive ctDNA result is highly specific and trustworthy, a negative result is simply 'not detected' and requires a tissue biopsy to definitively determine HER2 status for treatment decisions.
A common clinical practice—biopsying the primary tumor to guide treatment for metastatic disease—is considered biologically flawed. Metastases can have vastly different molecular and immune profiles from the primary tumor and from each other. Experts advocate for re-biopsying metastatic sites when feasible to get a more accurate profile of the progressing disease.
Instead of automatically ruling out immunotherapy for cancer patients with co-existing autoimmune diseases like rheumatoid arthritis, oncologists collaborate with experienced rheumatologists. This specialist team can assess the patient's specific condition, manage risks, and confidently advise whether it is safe to proceed with anti-PD-1 therapy, enabling more patients to access effective treatments.
Given that PD-L1 scores for gastroesophageal cancers can be exceptionally variable between labs, some clinicians prefer a simple CPS cutoff of 1. This 'some expression versus no expression' approach is considered more reproducible and practical for decision-making than relying on specific higher scores that may not be consistent across different testing sites.