Background The PIK3CA oncogene is one of the most mutated oncogenes in breast cancer, with ancestry-linked variations reported globally. The study aimed to discern the prevalence and prognostic role of PIK3CA mutations in Sri Lankan breast cancer patients for the first time, focusing on the correlation between somatic mutations and patient ancestry in an exclusively South Asian cohort of breast cancers. Materials & Methods A qPCR-based genetic analysis was performed on DNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples of 63 clinically diagnosed, female, Sri Lankan breast cancer patients using the QClamp® PIK3CA Mutation Detection Test for the hotspot mutations of PIK3CA (i.e., H1047R, E545K, E542K) followed by a statistical analysis. Patient samples and clinical data were fully anonymized, with no identifying information available to authors at any point of the study.  Results Somatic missense PIK3CA  mutations H1047R and E542K, were detected in 17.46% of the cohort. E545K mutation was not detected. The observed mutations were associated with an increased risk of lymph node (LN) metastasis (p=0.036, OR 9.60) and reduced recurrence-free survival (RFS) (p<0.001, HR 26.19). In addition, LN metastasis (p=0.026, HR 123.94) and a high Ki67 index (p=0.029, HR 79.69) were individually associated with reduced RFS. All three factors above- presence of a PIK3CA  mutation, LN metastasis and a high Ki67 index- in combination, were also associated with reduced RFS (p<0.001). Further analysis revealed a significant association between patient ancestry and PIK3CA mutation status (p=0.028). Conclusion Despite being a pilot study, the findings suggest that PIK3CA may serve as a potential prognostic biomarker in Sri Lankan breast cancer patients, with ancestry-linked variations potentially influencing metastatic outcomes. These results bring out the importance of integrating PI3K inhibitors into the therapeutic management of breast cancers in Sri Lanka after validating these findings in a functional study using a larger cohort.

The authors have declared no competing interest.

https://filgen.jp/Product/Bioscience4/DiaCarta/MAN.0017_IFU_QClamp_PIK3CA_Mutation_Detection_Test_RUO_Rev_3.pdf

https://www.qiagen.com/fi/resources/download.aspx?id=7d3df4c2-b522-4f6d-b990-0ac3a71799b6&lang=en

The author(s) received no specific funding for this work.

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Ethical approval for the analysis of an existing set of formalin-fixed paraffin-embedded (FFPE) breast tumor biopsy samples and fully anonymized medical records of the relevant patients was obtained from the Ethics Review Committee of the Institute of Biology, Sri Lanka (ERC IOBSL 303 07 2023, S1 Fig). Informed consent was not obtained from the patients as the patient clinical/follow-up data and patient samples were identified/analyzed exclusively using identification numbers assigned to each sample for the purpose of the research, thereby ensuring complete anonymity of patient identity. The authors did not have access to information that could identify individual participants during or after data collection, or at any point of the study.

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