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Overcoming Challenges in Biomarker Testing in Breast Cancer

Experts on breast cancer discuss challenges encountered in biomarker testing for patients with breast cancer.

This is a synopsis of an Insights series featuring Kevin Kalinsky, MD, MS, of Winship Cancer Institute of Emory University, and Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute.

Dr Erica Mayer and Dr. Kevin Kalinsky continued their discussion on evolving genomic profiling and treatment selection in hormone receptor-positive (HR+) metastatic breast cancer.

Dr Mayer highlighted challenges in circulating tumor DNA (ctDNA) testing, including low yield in minimal disease states like bone-only metastases. In such cases, she reflexes back to tumor tissue testing to evaluate targetable mutations like PIK3CA. Tumor biopsy is not always feasible, however, underscoring the utility of blood-based assays. Timing and logistics also pose challenges, as the multi-week turnaround for results does not align perfectly with clinical decision points about next treatment lines. However, Dr Mayer anticipates disease progression to mitigate these limitations.

Both speakers emphasized the value of recent ASCO [American Society of Clinical Oncology] guidelines recommending genomic profiling in HR+ metastatic breast cancer progressing on endocrine therapy. These evidence-based recommendations help establish testing as standard of care and facilitate insurance coverage.

Dr Mayer highlighted technical considerations in ctDNA assay selection, noting most assays used in metastatic disease evaluation take an agnostic approach detecting genome-wide alterations rather than tracking prespecified mutation panels informed by tumor tissue testing. This contrasts with ctDNA analysis in minimal residual disease assessment in early-stage patients, which often uses more personalized, tumor-informed assays. However, agnostic assays are emerging in this space as well.

Finally, the speakers concurred that serial ctDNA profiling over time is ideal given cancer genomic evolution with treatment pressure, which may uncover new targetable alterations not present earlier. As one example, Dr Mayer will evaluate for ESR1 mutations in patients who progress after multiple prior endocrine therapy lines, even with initially negative testing. Identifying late-arising ESR1 mutations may expand treatment options like selective estrogen receptor degraders.

Overall, Drs Kalinsky and Mayer advocate integrating plasma-based genomic cancer profiling into the continuum of HR+ metastatic breast cancer care. Serial liquid biopsy testing enables tracking of an adapting cancer genome, allowing for more timely, personalized therapeutic decisions as the disease landscape shifts.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.

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