Survival analysis of patients with early breast cancer associated with PIK3CA mutation

Abstract Purpose. The incidence of breast cancer (BC) with a mutation in the PIK3CA gene reaches 40% in luminal subtypes, where the disease is characterized by signs of hormone resistance. However, a comprehensive assessment of various clinicopathological factors is necessary for determining the prognosis and treatment plan of these patients. The objective of our study was to analyze the heterogeneity of the clinical course and outcomes of early breast cancer associated with PIK3CA mutation. Methods. A retrospective, prospective, single-center, noncomparative cohort study was conducted at the St. Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary". The analysis included 635 patients, 230 (36.2%) of whom had PIK3CA mutations. Radical surgical treatment was performed in 133 (57.8%) patients. Molecular genetic studies were conducted from January 2021 to March 2024. Clinical and morphological parameters and median relapse-free survival (mRFS) were assessed. Results.Frequent H1047, E542, and E545 mutations were found in 88.7% of patients and were associated with a better prognosis than rare mutations (mDFS 54 months vs 28 months, HR 0.57, log-rank p=0.38). At the time of primary diagnosis, the disease wasstage I in 9.2% of patients, stage II in 34.2%, stage III in 25.9%, and stage IV in 30.7%. The mRFS in the overall population of patients who underwent radical treatment was 62 months (95% CI 48-76). According to the univariate analysis, no statistically significant differences were found in the mRFS depending on the IHC profile (luminal A vs luminal B, p=0.62), the use of adjuvant radiotherapy (yes vs no, p=0.39), or the use ofbreast-conserving surgery or mastectomy (p=0.47). However, the use of perioperative chemotherapy compared to its absence (62 months vs 31 months, HR 0.26, log-rank p=0.01) and the choice of tamoxifen compared to aromatase inhibitors as adjuvant hormonal therapy (67 months vs 21 months, HR 0.17, log-rank p Conclusion. Hormone-resistant BC caused by PIK3CA mutation is highly heterogeneous and characterized by different disease courseand sensitivity to treatment.