دورية أكاديمية
Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007/150012; ACRIN 6657)
| العنوان: | Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence-free survival and development of bone metastases in I-SPY1 (CALGB 150007/150012; ACRIN 6657) |
|---|---|
| المؤلفون: | Vidula, Neelima, Yau, Christina, Li, Jiali, Esserman, Laura J, Rugo, Hope S |
| المصدر: | Breast Cancer Research and Treatment, vol 165, iss 1 |
| بيانات النشر: | eScholarship, University of California |
| سنة النشر: | 2017 |
| المجموعة: | University of California: eScholarship |
| مصطلحات موضوعية: | Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Aetiology, Biomarkers, Tumor, Bone Neoplasms, Breast Neoplasms, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Gene Expression Profiling, Humans, Logistic Models, Mastectomy, Middle Aged, Multivariate Analysis, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Oligonucleotide Array Sequence Analysis, Osteoprotegerin, Proportional Hazards Models, RANK Ligand |
| جغرافية الموضوع: | 129 - 138 |
| الوصف: | PurposeThe receptor activator of nuclear factor kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis may contribute to the development of bone metastases (BM). We studied gene expression in this pathway in primary breast cancer (BC) to determine correlations with clinical characteristics and outcomes in the neoadjuvant I-SPY1 study.MethodsWe evaluated RANK/RANKL/OPG expression using expression microarrays in I-SPY1 (n=149). Associations with clinical features were determined using t test and ANOVA. Associations between biomarker high versus low groups (dichotomized at an optimal cutpoint) and recurrence-free survival (RFS) were evaluated using the log-rank test and in a multivariate Cox proportional hazard model. A pooled external neoadjuvant cohort with gene expression data (GSE25066) (Hatzis et al. in JAMA 305(18):1873-1881, 30) (n=425) was used for validation. Associations with site-specific relapse were evaluated using the t-test and multivariate logistic regression adjusting for hormone receptor (HR) status.ResultsRANK was significantly higher in HR negative versus HR positive (p=0.027), in basal versus non-basal disease (p=0.004), and in those achieving pathologic complete response (p=0.038); the associations with HR negative and basal BC were also significant in GSE25066. In both datasets, higher RANK associated with significantly worse RFS (I-SPY1: p=0.045, GSE25066: p=0.044). However, this association did not remain significant after adjusting for HR status. In I-SPY1 patients with recurrence, higher RANK correlated with BM versus non-BM (p=0.045), even after adjusting for HR status (p=0.035).ConclusionsRANK is increased in HR negative and basal BC, and correlates with worse RFS and risk of BM. The RANK pathway is a potential therapeutic target in BC. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | qt4zc4z1xq; https://escholarship.org/uc/item/4zc4z1xqTest |
| الإتاحة: | https://escholarship.org/uc/item/4zc4z1xqTest |
| حقوق: | public |
| رقم الانضمام: | edsbas.5067AAB8 |
| قاعدة البيانات: | BASE |
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We studied gene expression in this pathway in primary breast cancer (BC) to determine correlations with clinical characteristics and outcomes in the neoadjuvant I-SPY1 study.MethodsWe evaluated RANK/RANKL/OPG expression using expression microarrays in I-SPY1 (n=149). Associations with clinical features were determined using t test and ANOVA. Associations between biomarker high versus low groups (dichotomized at an optimal cutpoint) and recurrence-free survival (RFS) were evaluated using the log-rank test and in a multivariate Cox proportional hazard model. A pooled external neoadjuvant cohort with gene expression data (GSE25066) (Hatzis et al. in JAMA 305(18):1873-1881, 30) (n=425) was used for validation. Associations with site-specific relapse were evaluated using the t-test and multivariate logistic regression adjusting for hormone receptor (HR) status.ResultsRANK was significantly higher in HR negative versus HR positive (p=0.027), in basal versus non-basal disease (p=0.004), and in those achieving pathologic complete response (p=0.038); the associations with HR negative and basal BC were also significant in GSE25066. In both datasets, higher RANK associated with significantly worse RFS (I-SPY1: p=0.045, GSE25066: p=0.044). However, this association did not remain significant after adjusting for HR status. In I-SPY1 patients with recurrence, higher RANK correlated with BM versus non-BM (p=0.045), even after adjusting for HR status (p=0.035).ConclusionsRANK is increased in HR negative and basal BC, and correlates with worse RFS and risk of BM. 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