Prognostic Impact of Homologous Recombination Deficiency in Triple-Negative Breast Cancer: A TCGA Analysis
Poster #: 006
Session/Time: A
Author:
Ria Rathore Kapoor, BS
Mentor:
Luisel Ricks-Santi, PhD
Research Type: TCGA Genomic Data and Clinical Data Analysis
Abstract
INTRODUCTION:
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and HER2 amplification. Homologous recombination deficiency (HRD), resulting from mutations in homologous recombination repair (HRR) genes, impairs DNA repair and is proposed as a prognostic and predictive biomarker in TNBC. However, its clinical relevance across broader breast cancer populations remains unclear. This study aimed to evaluate the association between HRD status and survival outcomes in TNBC and all other breast cancer subtypes using The Cancer Genome Atlas (TCGA) and multi-study breast cancer datasets available on cBioPortal.
METHODS:
Three cohorts were developed using a multi-study query of breast cancer datasets on cBioPortal: an all-subtype breast cancer cohort (n = 15,118), TNBC cases (n = 467), and invasive ductal carcinoma (IDC) subtype TNBC cases (n = 281). HRD-positive tumors were defined by the presence of pathogenic mutations in any of the following HRR genes: BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATM, ATR, CHEK2, BARD1, BRIP1, FANCA, FANCC, FANCD2, NBN, MRE11, and RAD50. Kaplan-Meier survival analyses were performed to estimate 60-month overall survival (OS) and relapse-free survival (RFS), stratified by HRD status, stage, grade, and molecular subtype. Analyses were conducted using R (version 4.5.0; R Foundation for Statistical Computing), with p-values computed using the log-rank test. Exploratory analyses of survival by treatment class were limited due to sparse data.
RESULTS:
HRD status was significantly associated with overall survival (OS) in the full breast cancer cohort (p < 0.0001), suggesting prognostic relevance across subtypes. However, HRD was not significantly associated with OS or RFS in TNBC (OS p = 0.42, RFS p = 0.11) or in the IDC-TNBC subset (OS p = 0.47, RFS p = 0.29). Among all breast cancer patients, stage (p < 0.0001), grade (p < 0.0001), and molecular subtype (p < 0.0001) were also significantly associated with OS. Analyses by treatment class were limited due to lack of therapy annotation, particularly for platinum agents and PARP inhibitors.
CONCLUSION:
HRD was significantly associated with OS in the broader breast cancer cohort, but not with survival outcomes in TNBC or IDC-TNBC subsets. These findings suggest that HRD may serve as a prognostic marker in breast cancer overall but is not predictive of survival in TNBC alone. Stage, grade, and molecular subtype remained robust prognostic indicators. The lack of treatment data in cBioPortal breast cancer datasets (e.g., platinum/PARP use) limits assessment of HRD's clinical utility in predicting therapy response.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptors (ER), progesterone receptors (PR), and HER2 amplification. Homologous recombination deficiency (HRD), resulting from mutations in homologous recombination repair (HRR) genes, impairs DNA repair and is proposed as a prognostic and predictive biomarker in TNBC. However, its clinical relevance across broader breast cancer populations remains unclear. This study aimed to evaluate the association between HRD status and survival outcomes in TNBC and all other breast cancer subtypes using The Cancer Genome Atlas (TCGA) and multi-study breast cancer datasets available on cBioPortal.
METHODS:
Three cohorts were developed using a multi-study query of breast cancer datasets on cBioPortal: an all-subtype breast cancer cohort (n = 15,118), TNBC cases (n = 467), and invasive ductal carcinoma (IDC) subtype TNBC cases (n = 281). HRD-positive tumors were defined by the presence of pathogenic mutations in any of the following HRR genes: BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATM, ATR, CHEK2, BARD1, BRIP1, FANCA, FANCC, FANCD2, NBN, MRE11, and RAD50. Kaplan-Meier survival analyses were performed to estimate 60-month overall survival (OS) and relapse-free survival (RFS), stratified by HRD status, stage, grade, and molecular subtype. Analyses were conducted using R (version 4.5.0; R Foundation for Statistical Computing), with p-values computed using the log-rank test. Exploratory analyses of survival by treatment class were limited due to sparse data.
RESULTS:
HRD status was significantly associated with overall survival (OS) in the full breast cancer cohort (p < 0.0001), suggesting prognostic relevance across subtypes. However, HRD was not significantly associated with OS or RFS in TNBC (OS p = 0.42, RFS p = 0.11) or in the IDC-TNBC subset (OS p = 0.47, RFS p = 0.29). Among all breast cancer patients, stage (p < 0.0001), grade (p < 0.0001), and molecular subtype (p < 0.0001) were also significantly associated with OS. Analyses by treatment class were limited due to lack of therapy annotation, particularly for platinum agents and PARP inhibitors.
CONCLUSION:
HRD was significantly associated with OS in the broader breast cancer cohort, but not with survival outcomes in TNBC or IDC-TNBC subsets. These findings suggest that HRD may serve as a prognostic marker in breast cancer overall but is not predictive of survival in TNBC alone. Stage, grade, and molecular subtype remained robust prognostic indicators. The lack of treatment data in cBioPortal breast cancer datasets (e.g., platinum/PARP use) limits assessment of HRD's clinical utility in predicting therapy response.