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The p160 ER co-regulators predict outcome in ER negative breast cancer

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Abstract

The SRC family of ER co-regulators are frequently overexpressed in breast cancer. Overexpression of AIB1 appears to be linked to hormone resistance in HER2 positive breast cancer. However, the role of these co-regulators in ER negative disease is poorly understood. SRC1, SRC2 and AIB1 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate tumours that overexpress both HER2 and AIB1 were associated with markedly reduced relapse free, distant relapse free and overall survival compared to HER2 and AIB1 only overexpressing tumours irrespective of ER status. In ER negative disease both SRC1 and AIB1 were linked to early relapse and death. The SRC family of ER co-regulators is involved in early relapse and resistance in both ER negative and ER positive breast cancer challenging the conventional concept that this effect is mediated solely via the ER.

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Conflict of interest

All authors state that they have no financial conflicts of interest.

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Authors and Affiliations

  1. Breakthrough Breast Cancer, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK

    Melanie Spears & John M. S. Bartlett

  2. Endocrine Cancer Research Group, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh, UK

    Melanie Spears, Mary Anne Quintayo, Johanna Pedraza, Alison F. Munro & John M. S. Bartlett

  3. Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, BCM 600, N1110, Houston, TX, 77030, USA

    Steffi Oesterreich, Ilenia Migliaccio, Carolina Guiterrez & Susan Hilsenbeck

  4. Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK

    Jeremy St. J. Thomas, Gill R. Kerr, Wilma J. L. Jack, Ian H. Kunkler, David A. Cameron & Udi Chetty

  5. Dipartimento di Scienze Biomorfologiche e Funzionali, Universita’ degli Studi di Napoli “Federico II”, Via Pansini 5, Naples, Italy

    Ilenia Migliaccio

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  1. Melanie Spears
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Correspondence to John M. S. Bartlett.

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Supplementary material 1 (DOC 35 kb)

10549_2011_1426_MOESM2_ESM.doc

Fig. 1 HER2 and SRC expression in ERα positive patients: Relapse free survival Kaplan–Meier survival curves (relapse free survival) for patients with tumours positive (expression of within upper quartile) for either SRCs (grey lines), HER2 (black dotted lines) or both HER2/SRC (grey dotted lines) or negative for both HER2/SRC (black lines). Y axis survival = proportion of patients event free overtime, X axis = duration of follow up (years). Panel A = HER2/AIB1, Panel B = HER2/SRC2, Panel C = HER2/SRC1 (DOC 49 kb)

10549_2011_1426_MOESM3_ESM.doc

Fig. 2 HER2 and SRC expression in ERα positive patients: distant relapse free survival Kaplan–Meier survival curves (distant relapse free survival) for patients with tumours positive (expression of within upper quartile) for either SRCs (grey lines), HER2 (black dotted lines) or both HER2/SRC (grey dotted lines) or negative for both HER2/SRC (black lines). Y axis survival = proportion of patients event free overtime, X axis = duration of follow up (years). Panel A = HER2/AIB1, Panel B = HER2/SRC2, Panel C = HER2/SRC1 (DOC 48 kb)

10549_2011_1426_MOESM4_ESM.doc

Fig. 3 HER2 and SRC expression in ERα positive patients: breast cancer specific survival: Kaplan–Meier survival curves (breast cancer specific survival) for patients with tumours positive (expression of within upper quartile) for either SRCs (grey lines), HER2 (black dotted lines) or both HER2/SRC (grey dotted lines) or negative for both HER2/SRC (black lines). Y axis survival = proportion of patients event free overtime, X axis = duration of follow up (years). Panel A = HER2/AIB1, Panel B = HER2/SRC2, Panel C = HER2/SRC1 (DOC 48 kb)

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Spears, M., Oesterreich, S., Migliaccio, I. et al. The p160 ER co-regulators predict outcome in ER negative breast cancer. Breast Cancer Res Treat 131, 463–472 (2012). https://doi.org/10.1007/s10549-011-1426-1

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  • DOI: https://doi.org/10.1007/s10549-011-1426-1

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