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

2021 ◽  
Author(s):  
Xiaoran Liu ◽  
Andrew A. Davis ◽  
Feng Xie ◽  
Xinyu Gui ◽  
Yifei Chen ◽  
...  
Keyword(s):  
Ethnic Groups ◽  
Hormonal Therapy ◽  
Hormone Receptor ◽  
Liquid Biopsy ◽  
Metastatic Breast ◽  
The United States ◽  
First Line ◽  
Hormone Receptor Positive ◽  
Genomic Landscape ◽  
The Us

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.

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

2021 ◽  
Author(s):  
Xiao-Ran Liu ◽  
Davis Andrew ◽  
Feng Xie ◽  
Xinyu Gui ◽  
Yifei Chen ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Progression Free Survival ◽  
The United States ◽  
Circulating Tumor Dna ◽  
Rank Test ◽  
First Line ◽  
Hormone Receptor Positive ◽  
Genomic Landscape

Abstract Purpose: Comparison of mutation landscape across ethnics using the identical detecting platform is important. We explored the differential genomic landscape of patients with hormone-receptor positive (HR+), HER2-negative MBC of first line recurrence or Stage IV at diagnosis from the United States (US) and China (CN).Methods: Twenty-seven US patients and 65 CN patients had circulating tumor DNA (ctDNA) sequencing from plasma using the harmonized CLIA-certified, 152-gene PredicineCareTM liquid biopsy assay. Clinical outcomes were correlated with ctDNA variants. Progression-free survival (PFS) was performed for patients and compared using log-rank test. Results: All patients from CN cohort received chemotherapy and/or hormonal therapy, while 85.2% (23/27) patients of US cohort hormonal plus CDK4/6 inhibitor. Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. Prevalence of AKT1(18.5% vs. 3.1%, P = 0.008) and CDH1 were higher in US cohort (18.5% vs. 1.5%, P = 0.021), and gain of FGFR1 was higher in the CN cohort (7.4% vs. 24.6%, P = 0.048). PTEN deletion (5.7 months vs. 13.2 months, P = 0.03) and ESR1 alterations (9.0 months vs. 13.2 months, P = 0.02) were associated with significantly shorter PFS in CN cohort. However, the similar result was not found in US cohort. Conclusions: Differential prevalence of FGFR1, AKT1, and CDH1 in HR+ MBC were found between US and CN, which indicates a slight difference in a genomic setting. Meanwhile, certain genes such as PTEN and ESR1 shows varied predictive value across US and CN cohort regarding PFS.

scholarly journals Cell-free DNA Comparative Analysis of Genomic Landscape of First-line Hormone-receptor Positive Metastatic Breast Cancer From US and China

2020 ◽  
Author(s):  
Xiao-Ran Liu ◽  
Andrew A. Davis ◽  
Feng Xie ◽  
Xinyu Gui ◽  
Yifei Chen ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Therapeutic Potential ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Progression Free Survival ◽  
The United States ◽  
Rank Test ◽  
Hormone Receptor Positive ◽  
Genomic Landscape ◽  
The Us

Abstract Background: The differential mutation landscape between ethnics is more comparable when using the identical detecting platform.We explored the differences in genomic landscape of patients with hormone-receptor positive (HR+), HER2-negative MBC of first recurrence or Stage IV at diagnosis from the United States (US) and China (CN).Methods: Twenty-seven US patients and 65 CN patients had circulating tumor DNA (ctDNA) sequencing from plasma using the harmonized CLIA-certified, 152-gene PredicineCareTM liquid biopsy assay. Clinical outcomes were correlated with ctDNA variants. Progression-free survival (PFS) and overall survival analysis was performed for patients and compared using log-rank test. Results: Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The most common mutations detected included TP53, PIK3CA, CDH1, AKT1, ESR1, and BRCA2 in both US and CN patients. AKT1(18.5% vs. 3.1%, P = 0.008) and CDH1 mutations were more frequent in the US population (18.5% vs. 1.5%, P = 0.021), and gain of FGFR1 was more common in the CN cohort (7.4% vs. 24.6%, P = 0.048). PTEN deletion (5.7 months vs. 13.2 months, P = 0.03) and ESR1 alterations (9.0 months vs. 13.2 months, P = 0.02) were associated with significantly shorter PFS in CN cohort. Conclusions: To our knowledge, this is the first real world study using a single harmonized ctDNA assay to profile plasma samples of patients from the US and CN. Differential prevalence of the mutations with therapeutic potential were found between US and CN.

Cell-free DNA comparative analysis of hormone receptor-positive, first-line metastatic breast cancer genomic landscape in the United States and China.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1059-1059
Author(s):  
Huiping Li ◽  
Andrew A. Davis ◽  
Xiao-ran Liu ◽  
Feng Xie ◽  
Xin-Yu Gui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
The United States ◽  
Chinese Patients ◽  
Hormone Receptor Positive ◽  
Genomic Landscape ◽  
The Us ◽  
Chinese Cohort

1059 Background: Metastatic breast cancer (MBC) is a heterogeneous disease associated with known somatic mutations of variable biological value in different subtypes. Furthermore, the clinical evolution of the disease demonstrates clonal evolution resulting in disease resistance more accurately detected using blood-based sequencing. Few studies have explored differences in genomic features of tumors across populations. Here, we performed circulating tumor DNA (ctDNA) sequencing to compare the genomic landscape of patients with hormone-receptor positive MBC at time of first recurrence or de-novo metastatic diagnosis in the United States (US) and China. Methods: Twenty-three US patients from Northwestern University and 65 Chinese patients from Peking University had ctDNA sequencing from plasma performed using the harmonized CLIA-certified, 152-gene PredicineCARE assay in laboratories in the US and China, respectively. The data analysis was conducted in China. Institutional Review Boards at each site approved the study. Fisher’s exact test was performed to compare mutational frequencies across populations. Results: Median age of patients at MBC diagnosis was 51 in the US cohort and 55 in the Chinese cohort. 87% of US patients and 82% of Chinese patients had received prior therapy for primary breast cancer, including endocrine therapy. Mutations were detected in 17 of 23 (74%) US patients and 59 of 65 (91%) Chinese patients. CNAs were observed in 57% of US patients and 58% of Chinese patients. The most common mutations detected in US patients were TP53 (26%), PIK3CA (22%), AKT1 (22%), CDH1 (17%), PTEN (13%), and ESR1 (9%) vs. PIK3CA (46%), TP53 (35%), ESR1 (12%), and BRCA2 (11%) in Chinese patients. Frequency of AKT1 and CDH1 mutations were significantly higher in the US population (P < 0.05), while PIK3CA mutations were higher in the Chinese population (P < 0.05). CNA gains in CCND3 and CDK4 were significantly higher in the US cohort, and FGFR1 was significantly more common in the Chinese cohort (all P < 0.05). Conclusions: To our knowledge, this is a first cross-regional comparison study in HR+ MBC patients in the US and China using a harmonized cfDNA NGS platform. At a population level, there were notable differences observed in somatic variants in two cohorts. Future sequencing efforts and clinical trials should include patients of diverse ethnic backgrounds to explore the impact of differences in genomic landscape on probability of benefit from treatments. A larger validation cohort is required to confirm these findings.

Disparities in treatment patterns and overall survival (OS) in hormone receptor-positive HER2+ metastatic breast cancer (MBC): A National Cancer Database Analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1032-1032 ◽  
Author(s):  
Abby Statler ◽  
Annie Gupta ◽  
Cassann N. Blake ◽  
Wei (Auston) Wei ◽  
Brian P Hobbs ◽  
...  
Keyword(s):  
Hormonal Therapy ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Treatment Patterns ◽  
Rank Test ◽  
National Cancer Database ◽  
First Line ◽  
Hormone Receptor Positive ◽  
Estrogen Receptor Positive ◽  
Line Setting

1032 Background: Determinants of variation in therapy utilization and OS are unclear for patients diagnosed with hormone receptor+, human epidermal growth factor 2 positive (HER2+) MBC. This study aimed to identify if there are disparities in first-line treatment patterns and outcomes for this subpopulation of MBC patients. Methods: We analyzed MBC patients included in the National Cancer Database diagnosed with estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+) and HER2+ disease (i.e. triple positive) treated with endocrine therapy or chemotherapy between 2010 and 2015. Analyses describe the distribution of treatments administered in the first-line setting. Kaplan-Meier method was used to estimate distributions of OS, which were compared among patient cohorts using the log-rank test. Results: Of the 6215 patients diagnosed with triple positive MBC, the majority were 50-70 years old (n=3414 [55%]), female (n= 6122 [98%]), and white (n=4478 [72%]). Four distinct treatment patters were identified; hormonal therapy was the most common (n= 2289 [37%]), followed by hormonal therapy + anit-HER2 (n=1471 [24%]), chemotherapy (1280 [20%]), and chemotherapy + anit-HER2 (n=1175 (19%)). Significant differences in demographic, socioeconomic, and disease characteristics were identified across groups. Disparities in OS were also observed; the unadjusted 5-year OS was substantially lower among older patients, African Americans (AA), those with government insurance, and lower income (Table). Conclusions: This is the first study to report disparities in treatment patterns and OS among real-world triple positive MBC patients. Further investigation is required to determine if there are independent causal associations between poor prognosis and the identified demographic and socioeconomic characteristics. [Table: see text]

First-line treatment with a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor for hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: Population-based outcomes for patients treated in Alberta, Canada.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13020-e13020
Author(s):  
Carla Pires Amaro ◽  
Atul Batra ◽  
Sasha M. Lupichuk
Keyword(s):  
Hormonal Therapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Population Based ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Hormone Receptor Positive ◽  
Targeted Agent ◽  
First Line Treatment

e13020 Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with an aromatase inhibitor (AI) has emerged as the standard first line treatment in patients with hormone receptor positive, human epidermal growth factor receptor-2 (HER-2) negative metastatic breast cancer (MBC). In this analysis, we describe population-based outcomes for first-line treatment with a CDK4/6i combined with an AI. Methods: All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 in a large Canadian province were included. Descriptive statistics were used to summarize patient demographics, tumor and treatment characteristics. Survival distributions were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) using a Cox proportional hazards model was constructed to examine associations between potentially prognostic clinical variables and progression free survival (PFS). Results: A total of 316 patients were included. Median age was 61 years (interquartile range, 53-70 years), 82% were postmenopausal women, 39% had de novo MBC, and 48% had non-visceral disease. Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib. The CDK4/6i was dose-reduced upfront or during treatment in 47%. While 70% of the patients discontinued treatment due to progression, 30% stopped due to toxicity/patient preference/physician recommendation. With a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7-NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45-3.88; P = 0.001) and dose reduction of the CDK4/6i (HR, 1.51; 95% CI, 1.06-2.16; P = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed (n = 131), 89% received second-line treatment (chemotherapy in 46%, single agent hormonal therapy in 35%, hormonal therapy plus a targeted agent in 15%, and other in 4%). Median time to progression on second line chemotherapy was 9.0 (5.8-17.6) months and second line hormonal therapy +/- targeted agent was 4.0 (3.4-8.6) months (P = 0.012). Conclusions: The real-world outcomes of first-line use of CDK4/6i and AI are encouraging. PR negative tumors and dose reduction appear to be negative prognostic markers. CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes.

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