Abstract P4-09-11: PIK3CA somatic alterations in 412 chinese invasive breast cancers: Higher frequency of mutant H1047R detected by next generation sequencing compared to breast cancer in caucasians

Abstract

Abstract Purpose: Somatic alterations of PIK3CA gene is an important therapeutic target in breast cancer (BC). The PI3Kα-specific inhibitor alpelisib was remarkably active against PIK3CA-mutated, HR-positive/HER2-negative BC in the SOLAR-1 trial. We hypothesized that PIK3CA alterations in Chinese BC patients across different molecular subtypes might differ from other ethnic groups and this information would be useful for selecting anti-PI3K therapy. Methods: The molecular profile of the PIK3CA gene was analyzed in 412 Chinese untreated invasive BC patients with ER/HER2 molecular subtypes, using a 540 gene next-generation sequencing panel. The results were compared to the molecular profile of Caucasian breast cancer patients in The Cancer Genome Atlas(TCGA-white). Results: Compared to wild type, PIK3CA alterations were more frequent in the ER+ subtype (49.3%, p=0.024), and tumors with low ki67 proliferation (58.3%, p=0.007) and low histological grade (grade I/II/III 80%, 53.4%, 35.9%, p<0.001). Compared to TCGA Caucasian race (TCGA-white), Chinese BC patients had a higher alteration frequency (45.6% vs. 34.7%, p<0.001). The p.H1047R mutation predominantly occurred among three hot spots (p.E545K, p.E542K and p.H1047R) for Chinese BC compared to that of the TCGA-white cohort (66.1% vs 43.7%, p=0.01). Nine novel mutation sites of PIK3CA were observed in the Chinese cohort that was absent among Caucasian BC patients. Among the four ER/HER2 molecular subtypes, ER+/HER2+ tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least (30.0%). However the latter presented the highest frequency of copy number amplification (19.05%). Conclusion: PIK3CA alterations prevail in nearly half of Chinese BC patients and has some different molecular features compared to that of Caucasian BC patients. The PIK3CA distribution patterns differed among four ER/HER2 subtypes. The results provide more insights for evaluating the results of PIK3CA inhibitors. Citation Format: Minghan Jia, Ning Liao, Bo Chen, Guochun Zhang, Yulei Wang, Xiaoqing Chen, Liping Guo, Li Cao, Hsiaopei Mok, Chongyang Ren, Kai Li, Cheukfai Li, Lingzhu Wen, Jiali Lin, Guangnan Wei, Zhou Zhang, Charles M Balch. PIK3CA somatic alterations in 412 chinese invasive breast cancers: Higher frequency of mutant H1047R detected by next generation sequencing compared to breast cancer in caucasians [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-11.