Association of preoperative and postoperative circulating tumour DNA (ctDNA) with PIK3CA gene mutation with risk of recurrence in patients with non-metastatic breast cancer

IF 2.3 4区医学 Q3 ONCOLOGY Surgical Oncology-Oxford Pub Date : 2024-03-05 DOI:10.1016/j.suronc.2024.102060

Fara Hassan , Jiang Huai Wang , Donal Peter O'Leary , Mark Corrigan , Henry Paul Redmond

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Abstract

Background

Circulating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer.

Methods

A cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (Post op) at either Post op time period; week 1–2, week 3–4 or weeks 5–12 were enrolled. PIK3CA gene mutations at exons 9 and 20 were detected in ctDNA with High resolution melting (HRM) PCR and Allele specific fluorescence probe-based PCR.

Results

A total of 62 patients (age, median (IQR), 51.50 (45.0–65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60–120 months) were enrolled. In total, 25 (40.3%) and 22 (35%) patients with breast cancer had detectable PIK3CA gene mutations in ctDNA in preoperative and postoperative period, respectively. PIK3CA gene mutations in ctDNA in postoperative period (hazard ratio (H.R: 18.05, p = 0.001) were a negative prognostic factor for recurrencefree survival (RFS) and overall survival (OS) (H.R: 11.9, p = 0.01) in patients with breast cancer. Subgroup analysis of ctDNA indicate that positive ctDNA in both preoperative/postoperative period and post op period only were found to have prognostic effect on RFS and OS (RFS; p < 0.0001, O·S; p = 0.0007). Moreover, ctDNA-based detection preceded clinical detection of recurrence in patients with an average lead time of 12 months (IQR:20–28.5 months) across all the breast cancer subtypes.

Conclusion

We highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in clinical practice

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术前和术后循环肿瘤 DNA (ctDNA) 与 PIK3CA 基因突变与非转移性乳腺癌患者复发风险的关系

循环肿瘤 DNA（ctDNA）在血液循环中含有肿瘤特异性基因突变，有助于对非转移性乳腺癌进行术后风险分层。在这项研究中，我们探讨了在乳腺癌患者术前（preop）和术后（postop）检测ctDNA中PIK3CA基因突变的可行性及其预后意义。一组接受根治性手术的乳腺癌患者在术前和术后（PO）的任一时间点（PO 第 1-2 周、PO 第 3-4 周和 PO 第 5-12 周）均可获得血液样本。采用高分辨熔融（HRM）PCR 和基于等位基因特异性荧光探针的 PCR 技术检测ctDNA 中 PIK3CA 基因第 9 和 20 号外显子的突变。共纳入 62 名患者（年龄中位数（IQR）为 51.50（45.0-65.0）岁），中位随访时间为 90 个月（四分位数间距（IQR）为 60-120 个月）。共有25名（40.3%）和22名（35%）乳腺癌患者在术前和术后的ctDNA中分别检测到了PIK3CA突变。术后ctDNA中的PIK3CA突变（危险比（H.R：18.05，P = 0.001）是乳腺癌患者无复发生存期（RFS）和总生存期（O-S）的负预后因素（H.R：11.9，P = 0.01）。ctDNA亚组分析表明，术前/术后ctDNA阳性和仅术后ctDNA阳性对RFS和O-S有预后影响（RFS：p < 0.0001，O-S：p = 0.0007）。此外，在所有乳腺癌亚型中，基于ctDNA的检测先于临床检测出患者的复发，平均提前时间为12.00个月（IQR:20-28.5个月）。我们强调了ctDNA对围术期乳腺癌患者的预后能力。不过，未来还需要进行前瞻性研究，以评估ctDNA在乳腺癌中的应用。

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来源期刊

Surgical Oncology-Oxford 医学-外科

CiteScore

4.50

自引率

0.00%

发文量

169

审稿时长

38 days

期刊介绍： Surgical Oncology is a peer reviewed journal publishing review articles that contribute to the advancement of knowledge in surgical oncology and related fields of interest. Articles represent a spectrum of current technology in oncology research as well as those concerning clinical trials, surgical technique, methods of investigation and patient evaluation. Surgical Oncology publishes comprehensive Reviews that examine individual topics in considerable detail, in addition to editorials and commentaries which focus on selected papers. The journal also publishes special issues which explore topics of interest to surgical oncologists in great detail - outlining recent advancements and providing readers with the most up to date information.