Background: The Phosphatidylinositol-4,5-bisphosphonate 3-kinase catalytic subunit alpha (PIK3CA) gene is mutated in about 30-40% of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) breast cancer (BC) patients. For HR+/HER2- advanced breast cancer patients with disease progression following endocrine-based therapy, the NCCN guideline recommends testing for PIK3CA mutations with tumour or liquid biopsy to identify suitable patients for targeted therapy with alpelisib, an oral α-specific PI3K inhibitor in combination with fulvestrant. The primary objective of this study was to evaluate the proportion and distribution of PIK3CA mutational landscape of HR+ve BC patients at the largest cancer centre in the United Arab Emirates (UAE). Material and methods: Retrospective review of consecutive HR+ve BC patients at Tawam Hospital for whom PIK3CA testing was requested. DNA was extracted from the samples and a targeted resequencing assay was used for mutation detection in exons 7, 9 and 20 of the PIK3CA gene. Sequencing was carried out using the Next Generation Sequencing platform Ion GeneStudio S5 Prime System with a detection limit of 2-5% of the mutant allelic content. Results: 124 patients with HR+ve BC were enrolled in the present study. The pathology samples were considered unsuitable/unsatisfactory in 18 cases. The median age was 51.5 years (range 31-90). All patients were female, 54% were post-menopausal and 49% presented with de-novo metastatic disease. Of the 106 eligible patients, PIK3CA mutations were detected in 33 (31%) patients, the most common being H1047R (45%) and E545K (30%) mutations in exons 20 and 9, respectively. Other less common mutations included C420R mutations (6%) in exon 7, E542 (6%) in exon 9 and H1047Y (3%) in exon 20. 9% of patients had more than one hotspot mutations, primarily in exons 9 and 20. Of the 12 HER2 +ve patients tested, 3 had PIK3CA mutations, most commonly the H1047R mutation in exon 20. Conclusion: The prevalence of PIK3CA mutations and the presence of most common hotspot mutations in exons 20 and 9 was consistent with prior published studies. The clinical relevance of PIK3CA mutations in HER2 +ve BC patients needs further assessment. Citation Format: Fathi Azribi, Mohammad Hourani, Sulaman Magdub, Aydah Alawadhi, Ali Yousif, Emad Dawoud, Khaled Al Qawasmeh, Mouza Al Ameri, Diaeddine Trad, Nouri Bennini, Mohamed Ahmed, Jawaher Ansari. PIK3CA mutation prevalence in hormone receptor positive breast cancer patients in United Arab Emirates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-04.
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