Relying solely on Next-Generation Sequencing (NGS) is insufficient for HER2 testing in biliary tract cancers. Data shows NGS misses up to 15% of patients with HER2 overexpression detected by immunohistochemistry (IHC). Performing both tests is essential to avoid denying patients effective targeted therapies.

There's a growing recognition that the molecular profile of a primary tumor can differ significantly from its metastases. To guide treatment more accurately, the preferred practice is to biopsy an accessible metastatic lesion when possible, as this better reflects the biology of the active disease being treated.

HER2 expression in cervical cancer can be heterogeneous and may emerge in metastatic sites even if the primary tumor was negative. Given the availability of effective HER2-targeting drugs, re-biopsying a metastatic focus is crucial to unlock previously unavailable treatment options for patients with recurrent disease.

Despite mutation testing being a critical first step for effective treatment planning in gastrointestinal stromal tumors (GIST), a significant number of patients in the United States still do not receive this essential diagnostic. This highlights a major gap between established best practices and real-world clinical application.

Patients with HER2-positive GI cancers can lose expression after treatment. While re-biopsy is ideal, it's often impractical or risky. In these cases, clinicians find ctDNA analysis of HER2 copy numbers to be a reliable alternative for guiding subsequent treatment decisions.

Unlike breast or lung cancer where a biomarker's effectiveness persists across treatment stages, biomarkers in upper GI cancers often fail to show similar efficacy when moved from one line of therapy to another. This suggests a more variable and rapidly changing tumor biology.

Post-treatment ctDNA positivity is a powerful predictor of high recurrence risk in gastric cancer patients. However, this advanced diagnostic knowledge creates a clinical dilemma, as there is no evidence-based consensus on how to act on the results, forcing clinicians to make treatment decisions without supporting data.

For patients with limited disease progression (oligoprogression) where radiation is the planned treatment, a repeat biopsy may be unnecessary. The result is unlikely to alter the immediate management plan, making the invasive procedure's risk-benefit ratio unfavorable in this specific clinical context.

The standard of care for GIST is evolving to mandate molecular testing at two key points: initial diagnosis and at the time of progression on first-line therapy. Using ctDNA at progression is now deemed critical to identify acquired resistance mechanisms, which directly informs the selection of subsequent, more effective therapies and avoids ineffective treatments.