Abstract PS3-05-06: Landscape of PIK3CA Mutations in Chinese Patients with Breast Cancer: A Multi-Center Real-World Study

Abstract Background: PIK3CA mutations are established therapeutic targets in breast cancer (BC). The population-level prevalence has been explored, but the distribution across key clinicopathological strata in Chinese patients (pts) remains to be elucidated. Methods: This retrospective study enrolled BC pts diagnosed between January 1997 and February 2025 with available PIK3CA testing (next-generation sequencing) results. Pts were divided based on PIK3CA mutation status into mutated and wild-type (WT) groups. Mutation status was defined as any positive test result during follow-up. Clinicopathological characteristics and prognosis were compared between the two groups. Results: This study enrolled 577 pts, divided into PIK3CA mutated group (n=226) and the WT group (n=351). PIK3CA mutation frequencies varied across molecular subtypes: highest in Luminal A (LA) (56.4%), followed in frequency by LB1 (45.8%), HER2-positive (45.5%), and Luminal B2 (LB2) (40.5%), but lower in triple-negative breast cancer (TNBC) (21.4%). Among mutated tumors, H1047R was predominant (42.5%), followed by E545K (17.7%) and E542K (11.5%). H1047R mutations showed higher prevalence in HER2+ (22.7% of HER2+ tumors) and LA (21.8%) subtypes compared to TNBC (11.7%). E545K mutations were enriched in LB2 (11.9%) and LA (11.5%) subtypes, while being rare in TNBC (2.8%). BRCA mutations were significantly less frequent in PIK3CA-mutated pts (mutated vs. WT: 4.0% vs. 16.2%, P<0.001), particularly BRCA1 (0.9% vs. 7.1%) and BRCA2 (3.1% vs. 10.3%). No significant differences were found in age, body mass index, menopausal status, family history, or clinical stage between two groups (all P>0.05) (Table 1). After a median follow-up of 38.2 months, no significant survival difference was observed. Five-year overall survival (OS) rates were 93.1% (95%CI: 88.9-97.5%) for the PIK3CA mutated group compared to 90.2% (95%CI: 85.9-94.8%) for the PIK3CA WT group. A molecular subtype-stratified survival analysis revealed that pts with the LA subtype harboring PIK3CA mutations had a 5-year OS rate of 92.5% (95% CI: 82.9-100.0%), while PIK3CA wild-type LA patients achieved a 5-year OS rate of 100.0% (95% CI: 100.0-100.0%) (P=0.035). In the stratification analysis of E545K, the PIK3CA WT group had a 5-year OS rate of 90.2% (95% CI: 85.9-94.8%). In contrast, pts with other PIK3CA mutations (non-E545K, n=186) achieved a 5-year OS rate of 95.3% (95% CI: 91.6-99.1%). The E545K mutation group (n=40) showed the lowest 5-year OS rate at 84.4% (95% CI: 71.1-100.0%). Conclusions: This real-world study identifies distinct clinicopathological profiles linked to PIK3CA mutations in Chinese BC pts, characterized by LA subtype enrichment and H1047R dominance. Notably, PIK3CA mutations are associated with poor survival in LA tumors and E545K mutations. These findings underscore the significant impact of PIK3CA mutations on the survival of Chinese BC pts. Citation Format: F. Xu, K. Jiang, R. Chen, H. Wu, Y. Zhong, H. Liu, W. Lyu, S. Mo, H. Chen. Landscape of PIK3CA Mutations in Chinese Patients with Breast Cancer: A Multi-Center Real-World Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-06.