Prevalence and prognosis of PIK3CA mutations in Bulgarian patients with metastatic breast cancer receiving endocrine therapy in first-line setting

R Gencheva; M Petrova; P Kraleva; S Hadjidekova; M Radanova; N Conev; D Stoyanov; J Arabadjiev; E Tazimova; S Bachurska; M Eneva; M Tsvetkova; G Zhbantov; T Karanikolova; D Manov; A Ivanova; M Taushanova-Hadjieva; R Staneva; E Dimitrova; I Donev

doi:10.1002/cnr2.1966

Prevalence and prognosis of PIK3CA mutations in Bulgarian patients with metastatic breast cancer receiving endocrine therapy in first-line setting

Cancer Rep (Hoboken). 2023 Dec 26;7(2):e1966. doi: 10.1002/cnr2.1966. Online ahead of print.

Authors

R Gencheva¹, M Petrova¹, P Kraleva¹, S Hadjidekova², M Radanova³, N Conev⁴, D Stoyanov⁴, J Arabadjiev⁵, E Tazimova⁵, S Bachurska⁶, M Eneva⁷, M Tsvetkova⁸, G Zhbantov¹, T Karanikolova¹, D Manov¹, A Ivanova¹, M Taushanova-Hadjieva¹, R Staneva², E Dimitrova³, I Donev¹

Affiliations

¹ Clinic of Medical Oncology, MHAT "Nadezhda", Sofia, Bulgaria.
² Department of Medical Genetics, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria.
³ Department of Biochemistry, Molecular Medicine and Nutrigenomics, Medical University of Varna, Varna, Bulgaria.
⁴ Clinic of Medical Oncology, University Hospital "St. Marina", Varna, Bulgaria.
⁵ Clinic of Medical Oncology, University Hospital Acibadem City Clinic Tokuda, Sofia, Bulgaria.
⁶ Department of General and Clinicalpathology, University Specialised Hospital for Oncology, Sofia, Bulgaria.
⁷ Department of Hospital Pharmacy "Nadezhda", Sofia, Bulgaria.
⁸ Medical Affairs, Novartis Bulgaria, Sofia, Bulgaria.

Abstract

Background and aims: In approximately 40% of patients with HER2-negative/HR-positive breast cancer tumors, the PIK3CA gene is mutated. Despite this, clinical outcomes vary between studies in this cohort. We aimed to ascertain the prevalence of PIK3CA mutations in patients with metastatic HR+/HER2- breast in Bulgaria, as well the evaluation and comparison of progression free survival (PFS) between wild-type (WT) and mutation-positive groups in the real-world setting.

Methods: Three oncology centers in Bulgaria collected 250 tissue samples between 2016 and 2022 for this multicentric retrospective study. PIK3CA mutations were identified using Real-Time qPCR. The median follow-up period was 35 months.

Results: The mean age of the mutant cohort was 57.6 ± 11.6 years, compared to 56.5 ± 12.2 years for the WT cohort (p = .52). The percentage of patients with visceral metastasis was 58.8% (n = 147). Approximately 84.3% (n = 210) of the patients had reached postmenopause. 29.2% (n = 73) of the patients had PIK3CA mutations. The predominant mutation was present in exon 20, H1047R (46.5%). We found a significant correlation only between the presence of a mutation and the metastatic diseases at diagnosis (p = .002). As first-line therapy, 67.1% of patients received endocrine therapy (ET) plus cyclin dependent kinase (CDK4/6) inhibitor, while the remainder received ET alone. The median PFS of patients in the group with the mutation was 32 months (95%, CI: 22-40) compared to 24 months in the WT cohort ((95%, CI: 21-36) (p = .45)); HR = 0.86 (95%, CI: 0.5-1.3) (p = .46). We corroborated our conclusion using propensity matching score analysis, (36 months [95% CI: 20-40] vs. 26 months [95% CI: 21-38], [p = .69]).

Conclusions: We found that the prevalence of PIK3CA mutations in our patients was comparable to what has been reported in other nations. Our results suggest that PIK3CA mutational status has no bearing to ET efficacy in first-line setting.

Keywords: PIK3CA (phosphatidylinosiol 3 kinase)-mutation; breast cancer; clinical outcome.