Medical Oncology Department, University Hospital of Salamanca, Salamanca, Spain.
Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
Cancer Med. 2024 Sep;13(17):e70101. doi: 10.1002/cam4.70101.
Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early-stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2- BC.
A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2- BC.
We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression-free survival (PFS) in PIK3CAm versus wild-type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08).
Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early-stage disease. Nonetheless, this should be validated in a prospective cohort study.
PIK3CA 基因热点（HS）突变可导致晚期乳腺癌（BC）的肿瘤学结局恶化和内分泌耐药，但它们在早期疾病中的预后作用仍存在争议。血浆和组织方法之间的总体一致性尚未得到充分探讨。我们的目的是对组织和血浆方法进行相关性分析，并分析 HR+/HER2-BC 中 PIK3CA 突变（PIK3CAm）的预后影响。
对 HR+/HER2-BC 患者的组织和血浆样本进行 Cobas®PIK3CA Mutation Kit 检测的回顾性单中心分析。
我们分析了 161 例 luminal BC 患者的 225 个样本。在 62 例患者中发现了 PIK3CA 突变（38.5%），其中 39.6%在组织中发现，11.8%在血浆中发现。在晚期疾病中，对 64 例患者进行了血浆和组织相关性分析，总体一致性为 70.3%。80 例患者接受 CDK4/6 抑制剂+内分泌治疗。与野生型（WT）相比，PIK3CAm 患者的无进展生存期（PFS）观察到中等程度的恶化（24m 与 30m；HR=1.39，p=0.26）。根据外显子 9 和 20 进行了亚分析，结果显示 PIK3CAm 外显子 9 与 20 人群的 PFS 统计学上更差（9.7m 与 30.3m；HR=2.84；p=0.024）。此外，与仅在组织中检测到 PIK3CAm 相比，在血浆中检测到 PIK3CAm 与更差的 PFS 相关（12.4 与 29.3；HR=2.4；p=0.08）。
我们的研究结果表明，组织中的 PIK3CA 评估是首选的诊断方法，然而，需要进一步的研究来提高液体活检在 PIK3CA 评估中的作用。PIK3CAm 在晚期 luminal BC 中表现出更差的结果，尤其是在外显子 9 突变携带者中，尽管存在内脏受累、内分泌治疗之前的暴露或在血浆中检测到 PIK3CAm，但在早期疾病中的预后仍不清楚。然而，这需要在前瞻性队列研究中进行验证。
