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Published on: July 25, 2020
Next-generation sequencing for PTEN testing in HR+/HER2- metastatic breast cancer
Nicola Fusco1, Umberto Malapelle2
1Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy.
Abstract:
Molecular alterations in the Phosphoinositide 3-kinase (PI3K) pathway are key drivers of tumorigenesis and progression in hormone receptor-positive, HER2-negative (HR+/HER2 -) metastatic breast cancer (MBC). These genomic changes are actionable through targeted therapeutic agents. In particular, access to these therapies depends on accurate molecular testing of PIK3CA, AKT1, and PTEN. Next-generation sequencing (NGS) has emerged as a transformative diagnostic tool, offering a comprehensive analysis of PI3K pathway alterations while concurrently evaluating other actionable markers, such as ESR1 and BRCA. Acknowledging its clinical importance, the European Society for Medical Oncology (ESMO) recommends NGS of tumor or plasma samples as the standard of care for patients with HR+ /HER2 - MBC. Although resource-intensive, NGS represents a significant advancement in MBC diagnostics, ensuring that therapeutic decisions are informed by a detailed and multidimensional molecular profile. This review highlights the capabilities of NGS for PI3K pathway testing in HR+ /HER2 - MBC, with a particular focus on the spectrum of PTEN alterations.
Insights
Accurate molecular testing for PIK3CA, AKT1, and PTEN alterations is crucial for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). Next-generation sequencing (NGS) provides comprehensive PI3K pathway analysis, guiding targeted therapy decisions.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Molecular alterations in the Phosphoinositide 3-kinase (PI3K) pathway are critical drivers in hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC).
- Targeted therapies exist for these genomic changes, but access relies on precise molecular testing of PIK3CA, AKT1, and PTEN.
- Next-generation sequencing (NGS) is a key diagnostic advancement for analyzing these PI3K pathway alterations.
Discussion:
- NGS enables comprehensive molecular profiling, including PI3K pathway mutations and other actionable markers like ESR1 and BRCA.
- The European Society for Medical Oncology (ESMO) endorses NGS for tumor or plasma samples as the standard of care in HR+/HER2- MBC.
- Despite resource intensity, NGS enhances diagnostic accuracy and informs multidimensional therapeutic strategies.
Key Insights:
- NGS is pivotal for identifying actionable PI3K pathway alterations in HR+/HER2- MBC.
- Accurate testing of PIK3CA, AKT1, and PTEN is essential for guiding targeted treatment selection.
- This review emphasizes the utility of NGS in evaluating the spectrum of PTEN alterations.
Outlook:
- Continued integration of NGS into clinical practice will refine treatment paradigms for MBC.
- Advancements in sequencing technology may improve accessibility and cost-effectiveness.
- Further research into the clinical significance of specific PI3K pathway alterations will optimize patient outcomes.
