PIK3CA Mutations as a Molecular Target for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer

• Published in: Frontiers in oncology Vol. 11; p. 644737
• Main Authors: Fusco, Nicola, Malapelle, Umberto, Fassan, Matteo, Marchiò, Caterina, Buglioni, Simonetta, Zupo, Simonetta, Criscitiello, Carmen, Vigneri, Paolo, Dei Tos, Angelo Paolo, Maiorano, Eugenio, Viale, Giuseppe
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 25-03-2021
• Subjects: biomarkers; breast cancer; HR+/HER2; Oncology; PIK3CA; RT-PCR; targeted therapy; targeted therapy; PIK3CA; next-generation sequencing; RT-PCR; biomarkers; HR+/HER2; breast cancer; liquid biopsy
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.644737

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
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.