Eduardo Terán, Rebeca Lozano, César A. Rodríguez, Mar Abad, Luis Figuero, José Antonio Muñoz, Belén Cigarral, Aline Rodrígues, Magdalena Sancho, M. Asunción Gómez, Daniel Morchón, Juan Carlos Montero, José María Sayagués, M. Dolores Ludeña, Emilio Fonseca
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引用次数: 0
Abstract
Introduction
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.
Methods
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.
Results
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).
Conclusions
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.
导言：PIK3CA 基因的热点（HS）突变可能会导致晚期乳腺癌（BC）较差的肿瘤预后和内分泌抵抗，但它们在早期疾病中的预后作用仍存在争议。血浆和组织方法的总体一致性尚未得到很好的探讨。我们的目的是将组织和血浆方法联系起来，分析PIK3CA突变（PIK3CAm）对HR+/HER2- BC预后的影响：用Cobas®PIK3CA突变试剂盒对HR+/HER2- BC患者组织和血浆样本中的PIK3CA突变状态进行回顾性和单中心分析：我们分析了来自161名腔隙性BC患者的225份样本。在62名患者（38.5%）中发现了PIK3CA突变，其中39.6%在组织中发现，11.8%在血浆中发现。在晚期疾病中，64 例患者进行了血浆和组织相关性分析，总体一致率为 70.3%。80例患者接受了CDK4/6抑制剂+内分泌治疗。我们观察到，PIK3CAm与野生型（WT）相比，无进展生存期（PFS）略差（24 m vs. 30 m; HR = 1.39, p = 0.26）。根据外显子9和20进行的子分析显示，PIK3CAm外显子9与20人群的PFS在统计学上较差（9.7 m vs. 30.3 m; HR = 2.84; p = 0.024）。此外，在血浆中检测到PIK3CAm与仅在组织中检测到PIK3CAm相比，PFS更差（12.4 vs. 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，但是还需要进行更多的研究，以提高液体活检在PIK3CA评估中的作用。PIK3CAm在晚期腔隙性BC中显示出更差的预后，尤其是在外显子9突变携带者中，尽管有内脏受累、之前接受过内分泌治疗或在血浆中检测到PIK3CAm，但早期疾病的预后尚不明确。不过，这一点应在前瞻性队列研究中得到验证。
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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