Plasma cell-free tumor DNA, PIK3CA and TP53 mutations predicted inferior endocrine-based treatment outcome in endocrine receptor-positive metastatic breast cancer

Q: What is the main purpose of the study?

To evaluate whether combining tumor burden and oncogenic genomic mutations can predict the outcome of endocrine-based therapy in ER-positive/HER2-negative metastatic breast cancer patients.

Q: How were cfDNA and mutations analyzed?

Blood samples collected prospectively before treatment were analyzed for cell-free tumor DNA using next-generation sequencing to detect PIK3CA hotspot and TP53 DNA-binding domain mutations.

Q: Which factors predicted a worse progression-free survival (PFS)?

High total cfDNA and the presence of PIK3CA or TP53 mutations were associated with worse PFS, and the adverse impact persisted even among patients with low tumor burden.

Sep 24, 2026

Uploaded by Aditya

Purpose examines how jointly accounting for tumor burden and oncogenic genomic mutations can predict outcomes of endocrine-based therapy in ER-positive/HER2-negative metastatic breast cancer. Method prospectively collected blood from 163 patients before treatment, then analyzed cell-free tumor DNA using next-generation sequencing to profile PIK3CA hotspot and TP53 DNA-binding domain mutations. Progression-free survival was tracked from therapy start to progression. Results show high cfDNA and PIK3CA/TP53 alterations predict worse PFS even with low tumor burden. Conclusion adjusting for cfDNA level links PIK3CA and TP53 mutations to detrimental endocrine-therapy outcomes, with allele frequency serving as a surrogate marker.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Introduction

Clinical need for tumor-burden estimation

Role of cfDNA and liquid biopsy

Significance of PIK3CA and TP53

Breast Cancer Research and Treatment (2023) 201:377–385 [https://doi.org/10.1007/s10549-023-06967-3](https://doi.org/10.1007/s10549-023-06967-3) Plasma cell‑free tumor DNA, PIK3CA and TP53 mutations predicted inferior endocrine‑based treatment outcome in endocrine receptor‑positive metastatic breast cancer Tom Wei‑Wu Chen1,2,3 · Wen Hsiao4 · Ming‑Shen Dai5 · Ching‑Hung Lin1,3 · Dwan‑Ying Chang1,3 · I‑Chun Chen1,2,3 · Ming‑Yang Wang6 · Shu‑Han Chang1 · Shu‑Min Huang1 · Ann‑Lii Cheng1,3 · Ko‑Wen Wu4 · Kien Thiam Tan4 · Yen‑Shen Lu1,3 Received: 18 January 2023 / Accepted: 3 May 2023 / Published online: 21 June 2023 © The Author(s) 2023 Abstract Purpose How to factor both tumor burden and oncogenic genomic mutations as variables to predict the outcome of endocrine-based therapy (ET) in ER-positive/HER2-negative metastatic breast cancer patients (MBC) remains to be explored. Method Blood samples prospectively collected from 163 ER-positive/HER2-negative female MBC patients, before ET, were used for cell-free tumor DNA (cfDNA) analysis. cfDNA was subjected to next-generation sequencing (NGS) to interrogate oncogenic PIK3CA hotspot and TP53 DNA-binding domain (DBD) mutations, including single nucleotide variants (SNVs) or small insertions and deletions (InDels) . The variant calling threshold was set at 0.5% . Progression-free survival (PFS) was measured from the start of the ET treatment to the time of disease progression of the same treatment regimen. Results Overall, the median PFS was 8.3 months (95% CI 5.7–11.1 months) . The median cfDNA was 38.5 ng (range 4.4– 1935 ng) . The proportion of patients with PIK3CA and TP53 alterations were 25.1 and 15.3%, respectively. Patients with high total cfDNA (HR 1.74, p = 0.003), PIK3CA mutation (HR 1.74, p = 0.007), and TP53 mutation (HR 1.64, p = 0.047) in liquid biopsy conferred worse outcome after ET. Even for patients with low tumor burden, the detrimental effect of PIK3CA or TP53 mutation remained significant (p < 0.001). For patients with either PIK3CA (p< 0.001) or TP53 mutation (p = 0.004), there was significant positive correlation between allele frequency (AF) and total cfDNA. Conclusion After adjustment of cfDNA level, PIK3CA and TP53 mutations observed in liquid biopsy exerted detrimental effects on the outcome of ET-based regimens. The AF ofPIK3CA or TP53 may be a surrogate marker for PFS. Keywords Liquid biopsy · Cell-free tumor DNA · Breast cancer · Endocrine receptor Introduction Kien Thiam Tan and Yen-Shen Lu contributed equally to this article. * Kien Thiam Tan [jtchen@actgenomics.com](jtchen@actgenomics.com) * Yen-Shen Lu [yslu@ntu.edu.tw](yslu@ntu.edu.tw) 1 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan 2 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan Despite the progress in the endocrine therapy (ET)-based regimens of endocrine receptor (ER)-positive human epidermal growth factor receptor (HER2)-negative metastatic breast cancer (MBC), the prognosis and the survival 3 Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan 4 ACT Genomics Co., Ltd, Taipei, Taiwan 5 Division of Hematology and Oncology, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan 6 Department of Surgery, National Taiwan University Cancer Center, Taipei, Taiwan outcome of different treatment regimens vary far and wide. A better estimate of treatment outcomes could facilitate communication of physicians and patients and the selection of the optimal treatment for these patients. Tumor burden plays a critical impact on prognosis but it may not be easily quantified and estimated for each patient. For ER-positive MBC patients, estimating tumor burden may be further complicated by the common involvement of bone metastases that is difficult to measure the extent and size of metastatic tumors. The genomic DNA of cancer cells could shed into

FAQs

What is the main purpose of the study?

To evaluate whether combining tumor burden and oncogenic genomic mutations can predict the outcome of endocrine-based therapy in ER-positive/HER2-negative metastatic breast cancer patients.

How were cfDNA and mutations analyzed?

Blood samples collected prospectively before treatment were analyzed for cell-free tumor DNA using next-generation sequencing to detect PIK3CA hotspot and TP53 DNA-binding domain mutations.

Which factors predicted a worse progression-free survival (PFS)?

High total cfDNA and the presence of PIK3CA or TP53 mutations were associated with worse PFS, and the adverse impact persisted even among patients with low tumor burden.

Sep 24, 2026

Uploaded by Aditya