ctDNA testing (liquid biopsy) is more effective than tissue biopsy for identifying ESR1 mutations. It samples DNA from all metastatic sites, capturing the disease's genetic heterogeneity and reflecting the most active resistance mechanisms, unlike a single-site needle biopsy which can miss them.

The personal genomics landscape is bifurcating. Direct-to-consumer companies offer broad, exploratory whole-genome sequencing for general interest, while clinician-mediated services provide targeted, actionable gene panels for specific medical conditions, creating distinct value propositions.

An individual tumor can have hundreds of unique mutations, making it impossible to predict treatment response from a single genetic marker. This molecular chaos necessitates functional tests that measure a drug's actual effect on the patient's cells to determine the best therapy.

In neoadjuvant therapy, a patient's long-term outcome is better predicted by stopping tumor DNA shedding (ctDNA clearance) than by achieving pathologic complete response (pCR), the traditional gold standard. This redefines what constitutes a successful treatment response before surgery.

The same cancer-driving mutation behaves differently depending on the cell's internal "wiring." For example, a drug targeting a mutation works in melanoma but induces resistance in colorectal cancer due to a bypass pathway. This cellular context is why genetic data alone is insufficient.

In a subset analysis of the high-risk MONARCH-E trial, an inferred Oncotype score did not identify which patients benefited from the CDK4/6 inhibitor abemaciclib. This indicates that while such scores assess prognostic risk and guide chemotherapy decisions, they are not predictive biomarkers for selecting patients for this targeted therapy.

Not all mutations are equal. PIK3CA alterations are often present from the start (truncal mutations), indicating a more aggressive cancer. In contrast, ESR1 mutations are typically acquired later as a direct mechanism of resistance to endocrine therapy, making repeat testing after disease progression crucial.

The RSClin tool integrates a patient's Oncotype DX score with their unique clinical-pathologic features, such as tumor size and grade. This provides a more accurate and personalized risk assessment, as the same genomic score can represent significantly different prognoses for patients who have low versus high clinical risk factors.

The technology for detecting cancer via cell-free DNA was discovered by accident. During non-invasive prenatal tests, some abnormal results weren't from the baby but from the mother's previously undiagnosed tumors shedding DNA, revealing an entirely new application for the technology.