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Review
. 2020 Sep;9(18):6463-6472.
doi: 10.1002/cam4.3278. Epub 2020 Jul 22.

Testing considerations for phosphatidylinositol-3-kinase catalytic subunit alpha as an emerging biomarker in advanced breast cancer

Deborah L Toppmeyer  1 , Michael F Press  2
Affiliations
Review

Testing considerations for phosphatidylinositol-3-kinase catalytic subunit alpha as an emerging biomarker in advanced breast cancer

Deborah L Toppmeyer et al. Cancer Med. 2020 Sep.

Abstract

Breast cancer is the most common cancer in women, and approximately 71% of carcinomas are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-not-amplified (HER2-negative). Pathogenesis of breast cancer is associated with dysregulation of several signaling pathways, including the phosphatidylinositol-3-kinase (PI3K) pathway. PIK3CA, the gene encoding PI3K catalytic subunit p110α, is mutated in 20%-40% of breast cancer patients. Several PI3K inhibitors have been developed and one, alpelisib, was recently approved for use in PIK3CA-mutated, HR+, HER2-negative advanced breast cancer. There are numerous types of assays and methods used in clinical studies to determine PIK3CA status in cancers. Additionally, there are several factors to consider for PIK3CA testing in clinical practice, including choice of assay, source of sample, and test timing. In this review, we discuss the use of PIK3CA as a biomarker to guide treatment decisions in patients with HR+, HER2-negative advanced breast cancer, as well as practical considerations and recommendations for testing.

Keywords: PIK3CA; advanced breast cancer; alpelisib; biomarker; companion diagnostic.

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Conflict of interest statement

The authors have disclosed the following potential conflicts of interest: Toppmeyer: Spouse employed by Merck; Press: Research grants to author's institution: Cepheid, Eli Lilly & Company, Novartis Pharmaceuticals, F. Hoffmann‐La Roche Ltd, Zymeworks; Consulting or advisory role with honoraria: Karyopharm Therapeutics, Puma Biotechnology, Biocartis, Eli Lilly & Company, Novartis Pharmaceuticals, F. Hoffmann‐La Roche Ltd; Expert testimony: Amgen; Travel, accommodations or expenses: Novartis.

Figures

Figure 1
Figure 1
Potential timepoints for tissue and liquid biopsy testing in HR+/HER2–ABC. ABC, advanced breast cancer; dMMR, mismatch repair deficient; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; MSI‐H, microsatellite instability‐high; PE, physical examination; PIK3CA, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha. †Otherbiomarkers:BRCA1/BRCA2, NTRK fusion, MSI‐H/dMMR. 30 ‡ therascreen ® PIK3CA RGQ PCR Kit (tissue and plasma) and FoundationOne® CDx(tissue). 47 , 55
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