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GRB7 protein over-expression and clinical outcome in breast cancer

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Abstract

The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values <0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07–2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16–2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89–100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0–15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer.

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Acknowledgments

The work is supported by Department of Veterans Affairs, Portland VA Research Foundation, OHSU Presidential Bridge Award, and OHSU Foundation. We are grateful to the technical assistance provided by the Histology Shared Resources at the Knight Cancer Institute, OHSU.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Betsy Ramsey & Edward Keenan

  2. Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, MC L586, Portland, OR, 97239, USA

    Tao Bai & Shiuh-Wen Luoh

  3. Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA

    Tao Bai & Shiuh-Wen Luoh

  4. Department of Medical and Molecular Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Amy Hanlon Newell & Susan Olson

  5. Department of Pathology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Megan Troxell

  6. Department of Public Health and Preventive Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Byung Park

  7. Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Betsy Ramsey, Tao Bai, Amy Hanlon Newell, Megan Troxell, Byung Park, Susan Olson, Edward Keenan & Shiuh-Wen Luoh

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  1. Betsy Ramsey
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Correspondence to Shiuh-Wen Luoh.

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Ramsey, B., Bai, T., Hanlon Newell, A. et al. GRB7 protein over-expression and clinical outcome in breast cancer. Breast Cancer Res Treat 127, 659–669 (2011). https://doi.org/10.1007/s10549-010-1010-0

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  • DOI: https://doi.org/10.1007/s10549-010-1010-0

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