Incorporating RNA-based Risk Scores for Genomic Instability to Predict Breast Cancer Recurrence and Immunogenicity in a Diverse Population

被引:2
|
作者
Hamilton, Alina M. [1 ]
Van Alsten, Sarah C. [2 ]
Gao, Xiaohua [2 ]
Nsonwu-Farley, Joseph [3 ]
Calhoun, Benjamin C. [1 ]
Love, Michael I. [4 ]
Troester, Melissa A. [1 ,2 ,6 ]
Hoadley, Katherine A. [5 ,6 ]
机构
[1] Univ North Carolina Chapel Hill, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA
[2] Univ North Carolina Chapel Hill, Gillings Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA
[4] Univ North Carolina Chapel Hill, Dept Biostat, Chapel Hill, NC USA
[5] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC USA
[6] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Computat Med Program, 116 Manning Dr,11212B Mary Ellen Jones,CB 7488, Chapel Hill, NC 27599 USA
来源
CANCER RESEARCH COMMUNICATIONS | 2023年 / 3卷 / 01期
关键词
TUMOR-INFILTRATING LYMPHOCYTES; EXPRESSION; CLASSIFICATION; CHEMOTHERAPY; ASSOCIATION; DEFICIENCY; LANDSCAPE; BLOCKADE; P53;
D O I
10.1158/2767-9764.CRC-22-0267
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Markers of genomic instability, including TP53 status and homologous recombination deficiency (HRD), are candidate biomarkers of immuno-genicity and immune-mediated survival, but little is known about the distribution of these markers in large, population-based cohorts of racially diverse patients with breast cancer. In prior clinical trials, DNA-based approaches have been emphasized, but recent data suggest that RNA -based assessment can capture pathway differences conveniently and may be streamlined with other RNA-based genomic risk scores. Thus, we used RNA expression to study genomic instability (HRD and TP53 pathways) in context of the breast cancer immune microenvironment in three datasets (total n = 4,892), including 1,942 samples from the Carolina Breast Can-cer Study, a population-based study that oversampled Black (n = 1,026) and younger women (n = 1,032). Across all studies, 36.9% of estrogen receptor (ER)-positive and 92.6% of ER-negative breast cancer had pres-ence of at least one genomic instability signature. TP53 and HRD status were significantly associated with immune expression in both ER-positive and ER-negative breast cancer. RNA-based genomic instability signatures were associated with higher PD-L1, CD8 T-cell marker, and global and multimarker immune cell expression. Among tumors with genomic insta-bility signatures, adaptive immune response was associated with improved recurrence-free survival regardless of ER status, highlighting genomic in-stability as a candidate marker for predicting immunotherapy response. Leveraging a convenient, integrated RNA-based approach, this analysis shows that genomic instability interacts with immune response, an impor-tant target in breast cancer overall and in Black women who experience higher frequency of TP53 and HR deficiency.Significance: Despite promising advances in breast cancer immunother-apy, predictive biomarkers that are valid across diverse populations and breast cancer subtypes are needed. Genomic instability signatures can be coordinated with other RNA-based scores to define immunogenic breast cancers and may have value in stratifying immunotherapy trial participants.
引用
收藏
页码:12 / 20
页数:9
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