PIK3CA Mutations as a Molecular Target for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer
Nicola Fusco1,2, Umberto Malapelle3, Matteo Fassan4,5
1Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Abstract:
Despite the significant achievements in the diagnosis and treatment of metastatic breast cancer (MBC), this condition remains substantially an incurable disease. In recent years, several clinical studies have aimed to identify novel molecular targets, therapeutic strategies, and predictive biomarkers to improve the outcome of women with MBC. Overall, ~40% of hormone receptor (HR)+/HER2- MBC cases harbor alterations affecting the (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. This pathway is a major target in oncogenesis, as it regulates growth, proliferation, cell survival, and angiogenesis. Lately, the pharmacologic targeting of PIK3CA in HR+/HER2- MBC has shown significant benefits after the occurrence of endocrine therapy resistance. The orally available α-selective PIK3CA inhibitor, alpelisib, has been approved in this setting. To perform an optimal patients' selection for this drug, it is crucial to adopt a tailored methodology. Clinically relevant PIK3CA alterations may be detected in several biospecimens (e.g. tissue samples and liquid biopsy) using different techniques (e.g. real-time PCR and next-generation sequencing). In this study, we provide an overview of the role of PIK3CA in breast cancer and of the characterization of its mutational status for appropriate clinical management.
Insights
Targeting PIK3CA mutations in hormone receptor-positive metastatic breast cancer (MBC) offers new hope. Identifying PIK3CA alterations is key for selecting patients who will benefit from targeted therapies like alpelisib.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic breast cancer (MBC) remains largely incurable despite treatment advances.
- Approximately 40% of hormone receptor-positive (HR+)/HER2-negative MBC cases have alterations in the PI3K/Akt/mTOR pathway.
- This pathway is crucial for cancer cell growth, proliferation, survival, and angiogenesis.
Purpose of the Study:
- To review the role of PIK3CA alterations in breast cancer.
- To discuss methods for characterizing PIK3CA mutational status.
- To highlight the importance of patient selection for targeted therapies.
Main Methods:
- Review of clinical studies and molecular pathway analysis.
- Discussion of diagnostic techniques for PIK3CA alterations, including real-time PCR and next-generation sequencing.
- Overview of therapeutic strategies targeting PIK3CA.
Main Results:
- PIK3CA pathway alterations are common in HR+/HER2- MBC.
- Targeting PIK3CA, particularly with alpelisib, shows benefits in endocrine-resistant cases.
- Accurate detection of PIK3CA mutations is essential for optimal patient selection.
Conclusions:
- PIK3CA is a significant therapeutic target in HR+/HER2- MBC.
- Tailored methodologies for PIK3CA mutation detection are crucial for clinical management.
- Characterizing PIK3CA status improves treatment outcomes for MBC patients.
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