Abstract 1752: Comprehensive genomic profiling of advanced breast cancer subtypes: Insights from liquid biopsy analysis and implications for personalized therapies
Authors: Liu Xiaoran , Liu Yaxin , Jia Cancan , Zhang Yue , Xie Feng , Tang Haoran , Jia Shidong , Li Huiping 
Published: March 2024

Abstract
Background: Breast cancer stands as the most prevalent malignancy affecting women’s health. The disease consists of three subtypes, including hormone receptor (HR) positive, HER2-positive, and triple-negative breast cancer (TNBC). In recent years, the advent of targeted therapies such as PI3K inhibitors has significantly improved the prognosis of breast cancer patients. However, the detection of relevant molecular markers, such as PIK3CA mutations, relies on tissue samples, which imposes limitations on the clinical application of these therapies. Consequently, this study presents a comprehensive analysis of genomic profiling that compares breast cancer patients across distinct pathological classifications, utilizing a liquid biopsy approach.
Methods: In this retrospective study, 214 patients with advanced breast cancer were recruited. Plasma samples collected prior to first line treatment were analyzed using PredicineCARE, a targeted next-generation sequencing (NGS) liquid biopsy assay, to detect somatic alterations in ctDNA of blood, including single nucleotide variations (SNVs), gene fusions, and copy number variations (CNVs).
Results: Based on the IHC classifications of tumor tissue, this cohort comprised 119 HR-positive, 61 HER2-positive, and 34 TNBC patients. The assay identified a total of 1456 mutations and 2357 gene copy number variants in plasma samples. Among these, the most frequently mutated genes and those with copy number variations (top 5) in HR-positive patients were TP53 (40%), PIK3CA (39%), ATM (22%), ERBB2 (19%), and FGFR1 (19%). In HER2-positive patients, they were TP53 (39%), PIK3CA (31%), ERBB2 (30%), NTRK1 (20%), and RAD50 (20%). For TNBC patients, the top genes were TP53 (59%), ERBB2 (44%), PIK3CA (35%), NTRK1 (35%), and BRCA2 (26%). Regarding the PIK3CA gene, the most prevalent mutation site was H1047, occurring in 12.61% of HR-positive patients, 14.75% of HER2-positive patients, and 11.76% of TNBC patients. Similarly, both E542 (4.20% in HR-positive, 3.28% in HER2-positive, and 2.94% in TNBC patients) and E545 (3.36% in HR-positive, 3.28% in HER2-positive, and 2.94% in TNBC patients) showed equivalent prevalence across the three classifications. These findings suggest the potential efficacy of PI3K inhibitors in various pathological types of breast cancer.
Conclusions: This study offers insights into the genomic landscape of advanced breast cancer subtypes through liquid biopsy. The observed prevalence of PIK3CA mutations supports the potential efficacy of PI3K inhibitors across these diverse types of breast cancer, laying the groundwork for personalized therapeutic strategies and biomarker identification for prognosis and targeted therapies.
Citation Format: Xiaoran Liu, Yaxin Liu, Cancan Jia, Yue Zhang, Feng Xie, Haoran Tang, Shidong Jia, Huiping Li. Comprehensive genomic profiling of advanced breast cancer subtypes: Insights from liquid biopsy analysis and implications for personalized therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1752.