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Relationship between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple-Negative Breast Cancer
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Abstract
Purpose: To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental Design: RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results: Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8–14.1] in the low and 20.4% (95% CI, 16.5–25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions: GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. Clin Cancer Res; 17(22); 7194–203. ©2011 AACR.
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GRB7 inhibition, either alone, in combination chemotherapy, or in combination targeted therapy improves the efficiency of antitumor therapy.
“GRB7 inhibition, either alone, in combination chemotherapy [39, 40], or in combination targeted therapy improves the efficiency of antitumor therapy.”
From Genome-wide CRISPR-cas9 knockout screening identifies GRB7 as a driver for MEK inhibitor resistance in KRAS mutant colon cancer (2022) · cites this paper as [40]
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“GRB7 inhibition, either alone, in combination chemotherapy [39, 40], or in combination targeted therapy improves the efficiency of antitumor therapy.”
Background
Metadata
- Authors
- Sparano, J. A., Goldstein, L. J., Childs, B. H., Shak, S., Brassard, D., Badve, S., Baehner, F. L., Bugarini, R., Rowley, S., Perez, E. A., Shulman, L. N., Martino, S., Davidson, N. E., Kenny, P. A., Sledge, G. W., & Gray, R.
- Affiliations
- Indiana University Health (US)
- Fox Chase Cancer Center (US)
- Corresponding author
- Sparano, Joseph A.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2011-11-14
- Volume
- 17
- Issue
- 22
- Pages
- 7194-7203
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC3570203
- OpenAlex
- W2116469621
- Cited by
- 22
- References
- 43
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Sanofi
- Northwestern University
- National Institutes of Health (5r01ca032012-03)
- Robert H. Lurie Comprehensive Cancer Center
- National Cancer Institute (U10CA066636, CA-23318, U10CA014958, (CA-25224, CA66636, CA32012, U10CA032291, U10CA025224, CA 32291, U24CA114737, U10CA086802, U10CA023318, U10CA021115, CA 21115)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Keywords
- Grb7, triple-negative breast cancer, adjuvant chemotherapy, doxorubicin, recurrence, prognostic factors, gene expression, anthracycline resistance, taxane resistance, therapeutic target
- MeSH terms
- Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Doxorubicin, Female, Humans, Middle Aged, Receptors, Estrogen, Receptors, Progesterone, Recurrence, Biomarkers, Tumor, Gene Expression, Chemotherapy, Adjuvant, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, GRB7 Adaptor Protein
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