Minghan Jia1, Ning Liao2,3,4, Bo Chen1, Guochun Zhang1, Yulei Wang1, Xuerui Li1, Li Cao1, Hsiaopei Mok1, Chongyang Ren1, Kai Li1, Cheukfai Li1, Lingzhu Wen1, Jiali Lin1,5, Guangnan Wei1,6, Charles M Balch7. 1. Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong, China. 2. Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, Guangdong, China. syliaoning@scut.edu.cn. 3. School of Medicine, South China University of Technology, Guangzhou, China. syliaoning@scut.edu.cn. 4. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China. syliaoning@scut.edu.cn. 5. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China. 6. School of Medicine, South China University of Technology, Guangzhou, China. 7. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abstract
PURPOSE: Somatic alteration of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a crucial therapeutic target in breast cancer (BC) and PI3Kα-specific inhibitor Alpelisib has been used in clinics. This study investigates the PIK3CA alterations in Chinese and Caucasians BC patients for the purpose of selecting anti-PI3K therapy. METHODS: The molecular profile of the PIK3CA gene was analyzed in 412 Chinese patients with untreated invasive BC using a 540 gene next-generation sequencing panel. The results were compared with data of the Caucasian BC patients in The Cancer Genome Atlas (TCGA-white). RESULTS: PIK3CA alterations were frequently found in BC of estrogen receptor (ER) positive (49.3%, p = 0.024), low ki67 proliferation index (58.3%, p = 0.007) and low pathological grade (grade I/II/III 80%, 53.4%, 35.9%, p < 0.001). Compared to TCGA-white, Chinese BC patients had a higher alteration frequency (45.6% vs. 34.7%, p < 0.001) with larger proportion of p.H1047R mutation among three common mutation sites (p.E545K, p.E542K and p.H1047R) (66.1% vs. 43.7%, p = 0.01). Across four molecular subtypes, ER + /human epidermal growth factor receptor 2 positive (HER2 +) tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least alteration (30.0%) but the most copy number amplification (19.05%). CONCLUSION: PIK3CA alterations prevail in Chinese BC patients and have different molecular features compared to that of Caucasians. The results provide precise annotations of PIK3CA genomic alterations of Chinese in the context of application of PIK3CA inhibitor.
PURPOSE: Somatic alteration of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a crucial therapeutic target in breast cancer (BC) and PI3Kα-specific inhibitor Alpelisib has been used in clinics. This study investigates the PIK3CA alterations in Chinese and Caucasians BC patients for the purpose of selecting anti-PI3K therapy. METHODS: The molecular profile of the PIK3CA gene was analyzed in 412 Chinese patients with untreated invasive BC using a 540 gene next-generation sequencing panel. The results were compared with data of the Caucasian BC patients in The Cancer Genome Atlas (TCGA-white). RESULTS:PIK3CA alterations were frequently found in BC of estrogen receptor (ER) positive (49.3%, p = 0.024), low ki67 proliferation index (58.3%, p = 0.007) and low pathological grade (grade I/II/III 80%, 53.4%, 35.9%, p < 0.001). Compared to TCGA-white, Chinese BC patients had a higher alteration frequency (45.6% vs. 34.7%, p < 0.001) with larger proportion of p.H1047R mutation among three common mutation sites (p.E545K, p.E542K and p.H1047R) (66.1% vs. 43.7%, p = 0.01). Across four molecular subtypes, ER + /humanepidermal growth factor receptor 2 positive (HER2 +) tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least alteration (30.0%) but the most copy number amplification (19.05%). CONCLUSION:PIK3CA alterations prevail in Chinese BC patients and have different molecular features compared to that of Caucasians. The results provide precise annotations of PIK3CA genomic alterations of Chinese in the context of application of PIK3CA inhibitor.
Entities:
Keywords:
Breast cancer; PIK3CA; Sequencing; Somatic alteration; TCGA