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. 2022 Dec;196(3):483-493.
doi: 10.1007/s10549-022-06637-w. Epub 2022 Oct 24.

PIK3CA-mutations in breast cancer

Kristin Reinhardt  1 , Kathrin Stückrath  1 , Carolin Hartung  1 , Sandy Kaufhold  1 , Christoph Uleer  2 , Volker Hanf  3 , Tillmann Lantzsch  4 , Susanne Peschel  5 , Jutta John  6 , Marleen Pöhler  7   8 , Marcus Bauer  9 , Friedrich Karl Bürrig  10 , Edith Weigert  11   12 , Jörg Buchmann  13 , Eva Johanna Kantelhardt  1   14 , Christoph Thomssen  1 , Martina Vetter  15
Affiliations

PIK3CA-mutations in breast cancer

Kristin Reinhardt et al. Breast Cancer Res Treat. 2022 Dec.

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 and methods: 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.

Keywords: Early breast cancer; PI3K; PIK3CA; Prognosis; Somatic mutations.

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Conflict of interest statement

CT reports reports support form: Martin Luther University Halle-Wittenberg, Arbeitsgemeinschaft Gynäkologische Onkologie e.V., American Diagnostica, BIOMED BMH4 - 98 - 9418, honoraria from: Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, NanoString, Novartis, Pfizer, Pierre Fabre, Puma, Sanofi-Aventis, Roche, Vifor, Seagen. All other authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Enrolment of patients of the PiA-cohort (n = 1270) and groups that were used for multivariate PIK3CA-mutation analyses (n = 1123) (bold)
Fig. 2
Fig. 2
Survival estimates for RFI and OS stratified by detection of PIK3CA-mutations. The tables present the effective sample size for each interval (numbers at risk). A, B All patients (n = 1123), RFI (A) and OS (B). C, D Patients with SHR-positive and HER2-negative tumours, Aromatase Inhibitors (AI) treatment (n = 208), RFI (C) and OS (D). E, F Patients with SHR-negative and HER2-negative tumours (TNBC) (n = 128), RFI (E) and OS (F)
Fig. 3
Fig. 3
Classification and Regression Tree (CART) for PIK3CA mutations. Bold arrows indicate the clinical value of PIK3CA mutations in subgroups
See this image and copyright information in PMC

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