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.

While liquid biopsies are a valuable, less invasive tool, a negative result is inconclusive for ruling out actionable mutations in NSCLC. It may simply mean the tumor isn't shedding enough DNA. Therefore, a negative liquid biopsy should never be the final word; it must be followed by a tissue biopsy to ensure patients don't miss out on targeted therapies.

Standard Next-Generation Sequencing (NGS) reports often just state "MET amplification" without a specific copy number. To make informed treatment decisions with MET inhibitors, clinicians must proactively contact the testing company's molecular pathology department to obtain this crucial, unlisted data point.

Dr. Wander favors liquid biopsies for tracking disease progression because they are safer and easier for patients. While acknowledging that tissue biopsies can sometimes detect mutations missed by liquid ones (10-30% discordance), he believes rapidly advancing technology will soon minimize these discrepancies, making them the standard for monitoring.

When a patient has a BRCA2 mutation, clinicians on the panel view it as such a dominant predictive biomarker that they would prioritize a PARP inhibitor-based triplet regimen. This single genetic finding often outweighs other clinical factors or even the potential addition of docetaxel in treatment decisions.

A positive genetic test does not automatically mandate the most aggressive surgery. For older patients, such as a 70-year-old with a new breast cancer and BRCA mutation, the clinical context—life expectancy, overall health—is paramount. A "knee-jerk" bilateral mastectomy may be overtreatment in such cases.

Treating genetic testing as a "magic" or specialized service reserved for counselors has caused a 30-year disservice to patients. This fear and hesitation has led to an estimated 38,000 missed opportunities annually to identify hereditary risk, resulting in larger cancers, harsher treatments, and more deaths.

For BRCA mutation carriers without cancer, the choice is not just about survival. While prophylactic mastectomy prevents most cancers, intensive screening with mammography and MRI detects cancers early enough that mortality rates are not significantly different. This allows patients to choose based on personal risk tolerance.

For critical driver mutations like ROS1 and ALK fusions, relying solely on DNA-based Next-Generation Sequencing (NGS) is insufficient. A study showed that a significant portion of these fusions are only detectable via RNA sequencing. Clinicians must verify that RNA analysis was included in NGS reports to avoid missing effective targeted therapies for one in five potential patients.