60P - A study of gene alterations in Asian patients with late stage and recurrent breast cancer

Background

Using liquid-based next generation sequencing (NGS) to detect circulating tumor DNA (ctDNA) and understanding genetic profiling has become more accessible recently. However, there is still limited prospective data in Asian breast cancer patients. This study is using Guardant360 to identify the genetic landscape of patients with recurrent breast cancer (BC) and de novo stage IV metastatic BC in an Asian population and to demonstrate genetic profile changes at disease progression.

Methods

Patients with either recurrent BC or de novo stage IV BC underwent both tissue-based NGS and liquid-based NGS before systemic therapy, and had liquid-based NGS done at PD. All patients were recruited from MacKay Memorial hospital from Jan 2020 to Dec 2021. The study was suspended in Jan 2022 due to restructuring of the sponsor’s organisation. Oncomine Comprehensive Assay was used for tissue based NGS, and Guardant360 was used for liquid based NGS.

Results

There were 44 patients (age range: 37-90 years old) recruited in the study, with 55 liquid samples (44 baseline and 11 PD samples), and 46 primary tissue samples or metastatic tissue samples in total. All the 46 tissue samples and all the 55 liquid samples were successfully sequenced. Out of the 44 liquid samples prior systemic therapy, ctDNA were detected in 84% (n=37) of the samples. Among of these 37 ctDNA positive samples, 64% of them have targetable alterations detected, including PIK3CA (31.8%, n=14), BRCA2 (20.5%, n=9), BRCA1 (9.1%, n=4), ERBB2 (4.6%, n=2), ESR1 (4.6%, n=2), FGFR2 amplification (4.6%, n=2), AKT1 (2.3%, n=1), and FGFR1 amplification (2.3%, n=1). In the study, we observed that higher percentage BRCA2/BCRA1 mutation was detected by liquid biopsy. A total of 31 patients underwent liquid and tissue NGS. We observed a high concordance in ESR1 alteration with 100%. Of the 12 patients with PIK3CA mutation detected in liquid and/or tissue, 8 were detected in both tissue and liquid, 2 detected in tissue alone and 2 detected in liquid alone.

Conclusions

Liquid-based NGS can be applied in clinical practice to identified clinically important mutations in Asian patients with recurrent breast cancer (BC) and de novo stage IV metastatic BC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

P-S. Yang.

Funding

Yonglin Foundation, Taipei, Taiwan.

Disclosure

All authors have declared no conflicts of interest.