PIK3CA-mutations in breast cancer.
Breast Cancer Res Treat
; 196(3): 483-493, 2022 Dec.
Article
en En
| MEDLINE
| ID: mdl-36279023
ABSTRACT
PURPOSE:
Phosphatidylinositide-3-kinase (PI3K) regulates proliferation and apoptosis; somatic PIK3CA-mutations may activate these processes. Aim of this study was to determine the prevalence of PIK3CA-mutations in a cohort of early stage breast cancer patients and the association to the course of disease. PATIENTS ANDMETHODS:
From an unselected cohort of 1270 breast cancer patients (PiA, Prognostic Assessment in routine application, NCT01592825) 1123 tumours were tested for the three PIK3CA hotspot-mutations H1047R, E545K, and E542K by qPCR. Primary objectives were the prevalence of somatic PIK3CA-mutations and their association to tumour characteristics. Secondary objective was the association of PIK3CA-mutations to recurrence-free interval (RFI) and overall survival.RESULTS:
PIK3CA-mutation rate was 26.7% (300 of 1123). PIK3CA-mutations were significantly more frequent in steroid hormone-receptor (SHR)-positive HER2-negative (31.4%), and G1 and G2 tumours (32.8%). Overall, we did not observe a significant association of PIK3CA-mutations to RFI. In SHR-positive BCs with PIK3CA-mutations, a strong trend for impaired RFI was observed (adjusted HR 1.64, 95% CI 0.958-2.807), whilst in SHR-negative BCs PIK3CA-mutations were insignificantly associated with improved RFI (adjusted HR 0.49; 95% CI 0.152-1.597). Of note, we observed a significantly detrimental prognostic impact of PIK3CA-mutations on RFI in SHR-positive, HER2-negative BCs if only aromatase inhibitors were administered as adjuvant therapy (adjusted HR 4.44, 95% CI 1.385-13.920), whilst no impact was observed in tamoxifen treated patients.CONCLUSION:
This cohort study speficies the overall mutation rate of PIK3CA in early breast cancer. The impact of PIK3CA-mutations on RFI and OS was heterogeneous. Our results suggest that estrogen deprivation failes to be active in case of PIK3CA-mutation.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
Tipo de estudio:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article