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Low SAFB levels are associated with worse outcome in breast cancer patients

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Abstract

The scaffold attachment factors SAFB1 and SAFB2 have been shown to function as estrogen receptor (ERα) co-repressors in breast cancer cells, and to affect many cellular processes such as stress response, RNA processing, and apoptosis. SAFB1 and SAFB2 have also been implicated in breast tumorigenesis: Their shared chromosomal locus at 19p13 is frequently lost in breast cancer, mutations have been identified, and overexpression results in growth inhibition. The purpose of this study was to determine SAFB1/SAFB2 protein expression in human breast tumors, to correlate their expression with either natural progression (“prognostic factor”) or with response to Tamoxifen (“predictive factor”), and to analyze potential correlations with tumor characteristics. SAFB1/SAFB2 protein were measured by immunoblotting using a pan-SAFB antibody in tumor extracts from patients with long-term clinical follow-up (n = 289), a subset of whom had received no adjuvant systemic therapy after breast cancer surgery (n = 117) and another subset of whom were treated with adjuvant Tamoxifen (n = 172). SAFB levels were correlated with clinico-pathological variables and patient outcome. SAFB levels varied widely, with 25 tumors not expressing detectable levels of SAFB. SAFB expression was significantly correlated with ERα, HER-2, bcl-2 and with expression of other ERα coregulators such as SRC-3. There was no association between SAFB expression and disease free survival, however, low SAFB expression was significantly associated with worse overall survival in patients who did not receive adjuvant therapy. This study shows that low SAFB protein levels predict poor prognosis of breast cancer patients, suggesting critical functions of SAFB1 and SAFB2 in breast cancer cells.

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Acknowledgments

We would like to thank the Breast Center Pathology and Biostatistics Core for their critical support of the study. The study was supported by NIH Program Project Grant P01 CA030195 and the Dr. Mildred Scheel Stiftung, Deutsche Krebshilfe (German Cancer Aid). Finally, I would like to thank Ms. Kaiyan Kang for technical support and Dr. Adrian Lee for input and comments on the manuscript.

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Authors and Affiliations

  1. Lester and Sue Smith Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Stephanie Hammerich-Hille, Susan G. Hilsenbeck, C. Kent Osborne & Steffi Oesterreich

  2. Department of Biostatistics, Institut Paoli Calmettes, Marseille, France

    Valerie J. Bardout

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  1. Stephanie Hammerich-Hille
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  2. Valerie J. Bardout
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  3. Susan G. Hilsenbeck
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  4. C. Kent Osborne
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  5. Steffi Oesterreich
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Correspondence to Steffi Oesterreich.

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Hammerich-Hille, S., Bardout, V.J., Hilsenbeck, S.G. et al. Low SAFB levels are associated with worse outcome in breast cancer patients. Breast Cancer Res Treat 121, 503–509 (2010). https://doi.org/10.1007/s10549-008-0297-6

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  • DOI: https://doi.org/10.1007/s10549-008-0297-6

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