496P - Comprehensive genomic profiling of advanced HR+/HER2- breast cancer patients using liquid biopsy

Background

Breast cancer is the most common cancer among women, and HR+/HER2- is the most frequent subtype. This type of cancer is characterized by a complex genomic landscape. However, obtaining tissue biopsies from patients with recurrent metastasis can be challenging. Moreover, previous liquid biopsy studies had limited success in detecting gene copy number loss. In this study, we present a comprehensive genomic profiling analysis of advanced HR+/HER2- breast cancer patients using liquid biopsy.

Methods

76 patients with advanced HR+/HER2- breast cancer were retrospectively recruited, and blood samples were collected prior to receiving chemotherapy or CDK4/6 inhibitor treatment. The study applied PredicineCARE, a targeted NGS liquid biopsy assay, to detect somatic alterations in ctDNA of blood.

Results

In total, 370 somatic mutations and 85 copy number variants were identified in 76 patients. The most commonly altered genes included TP53 (38%), PIK3CA (37%), ATM (24%), ESR1 (22%), FAT1 (22%), RAD50 (22%), and BRCA2 (17%). Among all patients, 27 were Ki67 negative, 43 were Ki67 positive, and the Ki67 status of 6 patients was unknown. The prevalence of NBN gene variations was significantly higher in the Ki67 positive group than in the Ki67 negative group (Ki67+: 8/43 vs. Ki67-: 0/27, p<0.05). Seventeen patients had metastasis at the time of initial diagnosis, among which the prevalence of FAT1 variations was significantly higher than that of non-metastasis patients (metastasis+ 10/17 vs. metastasis- 7/59, p<0.05). Of all 76 patients, 39 were treated with CDK4/6 inhibitors, and 37 were treated with chemotherapies. Patients treated with CDK4/6 inhibitors had a prolonged overall survival time compared to those treated with chemotherapies. The median overall survival time of the two groups was 38.7 months (chemotherapy) vs. not reached after 34.2 months (CDK4/6 inhibitors), p<0.001.

Conclusions

This study presents a comprehensive analysis of the mutational landscape of advanced HR+/HER2- breast cancer patients using liquid biopsy. Additionally, it compares the molecular profiles of patients with different clinical features receiving diverse treatments, thus identifying potential biomarkers for prognosis and targeted therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.