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PIK3CA-mutations in breast cancer
Kristin Reinhardt1, Kathrin Stückrath1, Carolin Hartung1
1Department of Gynaecology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
Breast Cancer Research and Treatment
|October 24, 2022
Summary
The PIK3CA mutation occurs in 26.7% of early breast cancers and its impact on recurrence-free survival is complex. Estrogen deprivation therapy may be less effective in PIK3CA-mutated tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Phosphatidylinositide-3-kinase (PI3K) pathway is crucial for cell proliferation and survival.
- Somatic mutations in the PIK3CA gene can lead to aberrant activation of this pathway.
- Understanding PIK3CA mutation prevalence and its clinical impact is vital for early-stage breast cancer management.
Purpose of the Study:
- To determine the prevalence of common PIK3CA hotspot mutations (H1047R, E545K, E542K) in a cohort of early-stage breast cancer patients.
- To investigate the association between PIK3CA mutations and tumor characteristics.
- To evaluate the impact of PIK3CA mutations on recurrence-free interval (RFI) and overall survival (OS).
Main Methods:
- Analysis of 1123 tumors from an unselected cohort of 1270 early breast cancer patients (PiA study).
- Quantitative PCR (qPCR) was used to detect three specific PIK3CA hotspot mutations.
- Statistical analysis was performed to assess mutation prevalence, association with tumor characteristics, RFI, and OS.
Main Results:
- PIK3CA mutations were detected in 26.7% (300/1123) of the tumors.
- Mutations were more frequent in steroid hormone-receptor (SHR)-positive, HER2-negative, and G1/G2 tumors.
- No significant overall association between PIK3CA mutations and RFI was observed, but a trend for impaired RFI in SHR-positive cases and improved RFI in SHR-negative cases was noted.
- A significantly detrimental impact on RFI was observed in SHR-positive, HER2-negative patients treated with aromatase inhibitors, but not with tamoxifen.
Conclusions:
- The study provides the overall mutation rate of PIK3CA in early breast cancer.
- The prognostic impact of PIK3CA mutations on RFI and OS is heterogeneous and context-dependent.
- Results suggest that estrogen deprivation may be less effective in PIK3CA-mutated breast cancers, particularly in certain subtypes.
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