Analysis of PIK3CA Mutations in Breast Cancer Subtypes

Abstract

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) is a central element of a signaling pathway involved in cell proliferation, survival, and growth. Certain mutations in this pathway result in enhanced PI3K signaling, which is associated with oncogenic cellular transformation and cancer. The aims of this study were to characterize different types of PIK3CA mutations in exons 9 and 20 in a series of primary breast carcinomas and to correlate the results with clinicopathologic parameters and survival. We used frozen tissue samples and sequenced exons 9 and 20 for a series of 241 patients with a diagnosis of breast carcinoma. We found that 15.8% of the primary breast carcinomas possessed PIK3CA mutations in either exon 9 or exon 20. The rate of PIK3CA mutations was increased in HR(+)/HER2(-) tumors (18.6%), but this difference did not reach a statistical significance. The lowest rate of mutations was observed in HR(+)/HER2(+) tumors (5.3%). No statistically significant association was found between the presence of PIK3CA mutations and the prognostic/clinical features of breast cancer, including histologic subtype, Her2 status, axillary lymph node involvement, tumor grade, and tumor stage. However, the presence of the H1047R mutation in 10 samples was associated with a statistically significantly worse overall survival. PIK3CA mutation was found to be a frequent genetic change in all breast cancer subtypes but occurred with the highest rate in HR(+)/HER2(-) tumors. Further studies are needed to validate the prognostic impact of different PIK3CA mutations.

Original paper Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting

“…We, similarly to other studies [24,26,28], did not find an association between PIK3CA mutation status and other clinical and biological parameters. However, there are reports in which the correlation between PIK3CA mutations and grade [26] or nodal status (in the ER-positive group) [27] was reported.…”

“…In our study we were able to detect 9/75 (12%) tumors with the H1047R mutation and 2/75 (2.7%) with the E545K mutation in the PIK-3CA gene. Our results are comparable to other studies, in which the mutated PIK3CA gene was found in 16%-24% of cases [22][23][24][25][26][27][28]. Comparing data with results obtained by other authors sometimes could be problematic because different mutations are investigated in groups of cancer patients with different clinical characteristics.…”

The potential role of leptin in tumor invasion and metastasis

“…In a study on 241 patients with breast cancer, PIK3CA mutations were found in 15.8% cases [69]. On the other hand, Firoozinia et al analyzed 50 breast cancer samples; 72% samples showed significant amplification of PIK3CA gene, while 24% exhibited protein overexpression [70].…”

Detection of PIK3CA Gene Mutations with HRM Analysis and Association with IGFBP-5 Expression Levels in Breast Cancer

“…The results have shown that corelation was present with lymph node metastases, and therapy response (Arsenic et al, 2014). PIK3CA mutations are common in hormone receptor positive and HER2-positive breast cancers (Stemke-Hale et al, 2008).…”