Dataset Information

Cell-free DNA comparative analysis of the genomic landscape of first-line hormone receptor-positive metastatic breast cancer from the US and China.

ABSTRACT:

Purpose

Meaningful comparison of mutational landscapes across ethnic groups requires the use of standardized platform technology. We have used a harmonized NGS-based liquid biopsy assay to explore the differential genomic landscape of patients with initially hormone receptor-positive (HR+), HER2-negative MBC of first line metastasis or primary Stage IV at diagnosis from the United States (US) and China (CN).

Methods

Plasma circulating tumor DNA (ctDNA) from 27 US patients and 65 CN patients was sequenced using the harmonized CLIA-certified, 152-gene PredicineCare™ liquid biopsy assay. Kaplan-Meier survival analysis was performed to analyze the correlation between genomic alterations and progression-free survival (PFS), and p-values were calculated using the log-rank test.

Results

All patients in the CN cohort received chemotherapy and/or hormonal therapy, while 85.2% (23/27) patients in the US cohort received hormonal therapy plus CDK4/6 inhibitors. Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The prevalence of AKT1 (P = 0.008) and CDH1 (P = 0.021) alterations were both higher in the US vs. CN cohort. In addition, FGFR1 amplification were more frequent in the CN vs. US cohort (P = 0.048). PTEN deletions (P = 0.03) and ESR1 alterations (P = 0.02) were associated with shorter PFS in the CN cohort, neither of these associations were observed in the US cohort. Interestingly, a reduced association between PTEN deletion and PFS was observed in patients receiving CDK4/6 inhibitor treatment.

Conclusion

The differential prevalence of ctDNA-based alterations such as FGFR1, AKT1, and CDH1 was observed in initially HR+/HER2- MBC patients in the US vs. CN. In addition, the association of PTEN deletions with shorter PFS was found in the CN but not the US cohort. The differential genomic landscapes across the two ethnic groups may reflect biologic differences and clinical implications.

SUBMITTER: Liu X

PROVIDER: S-EPMC8558197 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough endocrine therapy (ET) is the preferred option for hormone receptor-positive HER2-negative metastatic breast cancer (HR+/HER2- MBC), chemotherapy (CT) is still commonly used. The objective of this real-world study was to present the actual choice of first-line treatment for patients with HR+/HER2- MBC and evaluate the consistency with guidelines in China.MethodsPatients with HR+/HER2- MBC between 1996 and September 2018 were identified from of the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC). The statistical description was conducted to present the first-line treatment. Factors influencing the prescription of ET or CT were obtained using univariate and multivariate analysis. The consistency of the actual treatment with the guideline of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC guideline) was evaluated.ResultsOf 1,877 patients, 662 (35.3%) received ET, and 1,215 (64.7%) received CT. ET proportion was only 25.4% in 1996-2005 and gradually increased to 44.6% in 2016-2018. Aromatase inhibitors (69% of ET) and taxane-based regimens (66% of CT) were the most commonly used ET and CT, respectively. Univariate and multivariate analysis showed that patients with age ≥60, distant relapse-free interval (DRFI) ≥24 months, ER+/PR+, bone metastasis only, or progression on (neo)adjuvant ET were preferably chosen for ET as first-line treatment. Factors associated with preferring CT were de novo stage IV, liver or lung metastasis. 17.2% of patients (322 cases) who had neither visceral metastasis nor progression on (neo)adjuvant ET wrongly received CT instead of ET, which is inconsistent with CSCO BC guideline. More than half of patients receiving CT discontinued their initial treatment due to adverse events and other non-disease progression reasons.ConclusionsAlthough high proportion of HR+/HER2- MBC patients received CT as first-line treatment in China, it is gratifying to see that the proportion of patients receiving ET has gradually increased. Our study revealed that 17.2% of patients were over-treated according to CSCO BC guideline, which may provide data to promote guideline adherence. The clinical application for ET should be appropriately expanded in first-line treatment, especially for patients without visceral disease and proof of endocrine resistance.