PIK3CA somatic alterations in invasive breast cancers: different spectrum from Caucasians to Chinese detected by next generation sequencing

Abstract

Purpose Somatic alteration of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a crucial therapeutic target in breast cancer (BC) and PI3Kα-specific inhibitor Alpelisib has been used in clinics. This study investigates the PIK3CA alterations in Chinese and Caucasians BC patients for the purpose of selecting anti-PI3K therapy. Methods The molecular profile of the PIK3CA gene was analyzed in 412 Chinese patients with untreated invasive BC using a 540 gene next-generation sequencing panel. The results were compared with data of the Caucasian BC patients in The Cancer Genome Atlas (TCGA-white). Results PIK3CA alterations were frequently found in BC of estrogen receptor (ER) positive (49.3%, p = 0.024), low ki67 proliferation index (58.3%, p = 0.007) and low pathological grade (grade I/II/III 80%, 53.4%, 35.9%, p < 0.001). Compared to TCGA-white, Chinese BC patients had a higher alteration frequency (45.6% vs. 34.7%, p < 0.001) with larger proportion of p.H1047R mutation among three common mutation sites (p.E545K, p.E542K and p.H1047R) (66.1% vs. 43.7%, p = 0.01). Across four molecular subtypes, ER + /human epidermal growth factor receptor 2 positive (HER2 +) tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least alteration (30.0%) but the most copy number amplification (19.05%). Conclusion PIK3CA alterations prevail in Chinese BC patients and have different molecular features compared to that of Caucasians. The results provide precise annotations of PIK3CA genomic alterations of Chinese in the context of application of PIK3CA inhibitor.

PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer

“…These interesting findings in experimental research need to be linked to clinical practice. A recent study involving a cohort containing 412 Chinese patients with invasive breast cancer revealed that Chinese patients had a higher PIK3CA alteration frequency (45.6% vs. 34.7%; P < 0.001) compared to Caucasians in The Cancer Genome Atlas (TCGA) ( N = 453), indicating that an alteration in PIK3CA deserves greater attention among Chinese patients [ 43 ]. PIK3CA mutations have also been observed more frequently in the luminal type than in the basal-like breast cancers.…”

Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations

“…Additionally, compared with patients of EUR ancestry, patients of EAS ancestry with HER2+ BC and TNBC, as well as patients of SAS ancestry with HER2+ BC, were more likely to have tumors that harbor PIK3CAmut (Figs 2A, 2C and 2E). The ancestry-specific tumor PIK3CAmut prevalences observed across BC subtypes is supported by the findings from studies that sampled substantially fewer participants in Africa, [36][37][38][39] Latin America, [40][41][42][43][44] China or Korea, [45][46][47][48][49][50][51][52] and South Asian countries. [53][54][55][56][57] Inconsistencies between PIK3CAmut prevalences identified in our study and those reported in the literature were observed when sample sizes were small and when differences existed in the clinical characteristics of the populations evaluated and/or assay methodologies.…”

Syringin exerts anti-breast cancer effects through PI3K-AKT and EGFR-RAS-RAF pathways

“…PIK3CA is a subtype of PI3K, which encodes P110 α protein. In tumor cells, AKT is prone to mutate and continuously stimulates downstream genes, to increase the ability of cell invasion and metastasis [ 40 ]. RAS is known to regulate the expression of PI3K, which enhances the connection between the two pathways [ 41 ].…”