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.

Effective treatment of HER2-driven NSCLC requires more than just identifying mutations. HER2 is a multiplexed biomarker where both genetic mutations (TKD and non-TKD) and protein overexpression (via IHC) are independently actionable. Comprehensive testing is crucial to ensure patients are eligible for the full range of available targeted therapies, including TKIs and ADCs.

Shifting from clinician-ordered to pathologist-initiated reflex testing for NSCLC biomarkers combines diagnosis and molecular analysis into one workflow. This operational change minimizes delays, increases testing rates, and optimizes the use of small biopsy samples, getting actionable results to oncologists faster.

To qualify patients for HER2-directed therapies, clinicians pragmatically review all available historical biopsies (e.g., from the primary tumor or a prior recurrence). If any sample shows a positive result, they use it to justify insurance approval. This strategy prioritizes getting the patient the drug and avoids the need for a new, potentially invasive biopsy on the current metastatic lesion.

To reduce treatment delays, pathologists should initiate biomarker testing reflexively. Waiting for a medical oncologist to order tests at a first visit is a system failure, wasting critical time and risking the need to retrieve archived samples.

To avoid the inefficiency of re-requesting tests, some hospital labs now run a full panel of biomarkers (MMR, p53, HER2) on all endometrial cancer cases upfront. This operational decision standardizes the process, even if not every marker is immediately relevant for all histologies, preventing downstream delays and extra work for pathologists.

Rather than passively waiting for orders, nurses can actively check patient charts for required tests (HRD, Folate Receptor Alpha, HER2, PD-L1) and remind the physician, preventing treatment delays and ensuring access to targeted therapies.

Clinicians are pushing back against simple "negative" HER2 pathology reports, demanding detailed Immunohistochemistry (IHC) scores (0, 1+, 2+, 3+) and the criteria used. This granular data is crucial for determining eligibility for modern treatments like antibody-drug conjugates (ADCs), where even low protein expression can be clinically relevant and actionable for patient care.

Due to selective pressure from first-line treatment, 30-40% of HER2-positive gastroesophageal cancers lose HER2 expression by the time of progression. It is crucial to re-test these patients, either via tissue biopsy or ctDNA, to confirm continued HER2 positivity before initiating second-line HER2-targeted therapy like TDXD.