Data Sheet 1_Subtype-specific prognostic implications of plasma-detected PIK3CA mutations in Vietnamese breast cancer patients.docx

BackgroundPIK3CA mutations are among the most frequent genomic alterations in breast cancer (BC), contributing to disease progression and therapeutic resistance. Non-invasive blood assays can reveal tumor-specific DNA alterations, enhancing personalized oncology.
AimThis study aims to investigate the clinical relevance of plasma-detected PIK3CA mutations in Vietnamese breast cancer patients, with a focus on subtype-specific outcomes.
MethodsPIK3CA hotspot mutations (H1047R and E545K) were detected in plasma from 196 BC patients. Associations with clinicopathological features and progression-free survival (PFS) were assessed.
ResultsPIK3CA mutations were identified in 42.9% of patients with H1047R (31.6%) more prevalent than E545K (15.3%). Mutation rates were highest in HR+ subtypes and elevated in advanced or irradiated patients (p = 0.009). E545K was enriched in HR+ cases, while H1047R was more frequent in HER2+ tumors following radiotherapy. Among metastatic BC patients, those with PIK3CA mutations had shorter PFS (median, 7.0 vs. 15.0 months; p = 0.022), and univariate Cox regression showed increased progression risk (HR = 2.16), although not significant after multivariate adjustment. E545K was associated with lung (p = 0.047) and bone metastases (p = 0.012) and H1047R was enriched in brain metastases (p = 0.028).
ConclusionPlasma-detected PIK3CA mutations, particularly E545K and H1047R, exhibited subtype-specific associations with clinical outcomes, indicating that plasma analysis may provide complementary information for prognostic assessment in metastatic BC.

背景：PIK3CA突变是乳腺癌（breast cancer, BC）中最常见的基因组改变之一，可促进疾病进展与治疗抵抗。非侵入性血液检测可检出肿瘤特异性DNA改变，为个性化肿瘤诊疗提供支持。
目的：本研究旨在探究越南乳腺癌患者血浆检出的PIK3CA突变的临床相关性，并重点分析其与分子亚型特异性预后的关联。
方法：本研究在196例乳腺癌患者的血浆样本中检出了PIK3CA热点突变（H1047R与E545K），并评估了该突变与临床病理特征以及无进展生存期（progression-free survival, PFS）的相关性。
结果：42.9%的患者检出PIK3CA突变，其中H1047R突变占比31.6%，较E545K突变（15.3%）更为常见。激素受体阳性（hormone receptor positive, HR+）亚型患者的突变检出率最高，晚期或接受过放疗的患者突变率显著升高（p=0.009）。E545K突变在HR+病例中富集，而放疗后人表皮生长因子受体2阳性（human epidermal growth factor receptor 2 positive, HER2+）肿瘤中H1047R突变更为频发。在转移性乳腺癌患者中，携带PIK3CA突变者的无进展生存期更短（中位值：7.0个月 vs 15.0个月；p=0.022）；单变量Cox回归分析显示其疾病进展风险升高（风险比（hazard ratio, HR）=2.16），但经多变量校正后该差异无统计学意义。E545K突变与肺转移（p=0.047）和骨转移（p=0.012）相关，而H1047R突变在脑转移患者中富集（p=0.028）。
结论：血浆检出的PIK3CA突变，尤其是E545K与H1047R突变，与临床结局存在亚型特异性关联，提示血浆检测可为转移性乳腺癌患者的预后评估提供补充信息。