Breast Cancer Research and Treatment

, Volume 126, Issue 2, pp 395–405 | Cite as

Nuclear and cytoplasmic expressions of ERβ1 and ERβ2 are predictive of response to therapy and alters prognosis in familial breast cancers

  • Max YanEmail author
  • Mukta Rayoo
  • Elena A. Takano
  • kConFab Investigators
  • Stephen B. Fox
Preclinical study


Estrogen receptor (ER) α has been studied extensively in familial breast cancers but there are limited data on ERβ and its isoforms. This is an important issue since many BRCA1-associated tumours are “triple negative” and are resistant to conventional and targeted therapies. We performed an immunohistochemical study of pan-ERβ, ERβ1 and ERβ2 in a cohort of 123 familial breast carcinomas (35 BRCA1, 33 BRCA2 and 55 BRCAX) using a cut-off for positivity at 20% (Shaaban et al. in Clin Cancer Res 14:5228–5235, 2008). BRCA1 cancers were more likely to be nuclear ERα negative and nuclear pan-ERβ positive (21/32, 66%) when compared with BRCA2 (2/29, 7%) and BRCAX cancers (11/49, 22%) (both P < 0.001). For survival analysis, expression was also stratified using cut-offs defined by Bates et al. (Breast Cancer Res Treat 111:453–459, 2008) (score out of 7). Cytoplasmic ERβ2 expression correlated with shorter overall survival at 15 years regardless of cut-off used (both P < 0.046) At a cut-off score of 6 out of 7, cytoplasmic ERβ2 expression correlated with a poorer response to chemotherapy in both univariate (P = 0.011) and multivariate analyses including grade, lymph node status and chemotherapy as an interaction variable (P = 0.045, Hazard ratio 1.22, 95% CI 1.004–9.87). A similar trend was seen in a univariate analysis with a cut-off of 20% although this did not reach statistical significance (P = 0.057). Expression of nuclear ERβ1 was associated with a favourable response to endocrine therapy at 15 years regardless of cut-offs employed (both P < 0.025). However, this did not reach statistical significance in a multivariate analysis (P > 0.05). Since a significant proportion of ERα negative familial breast carcinomas are positive for nuclear ERβ1 and cytoplasmic ERβ2, the different ERβ isoforms and their intracellular location may need to be assessed, to identify patients that may benefit from hormonal and chemotherapy.


ERβ Breast BRCA1 BRCA2 BRCAX Familial breast carcinoma 



We wish to thank Heather Thorne, Eveline Niedermayr, the kConFab research nurses and staff, the staff and of the Family Cancer Clinics, the Clinical Follow Up Study (funded by NHMRC Grants 145684, 288704 and 454508). kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. This study was partly funded by the Victorian Breast Cancer Research Consortium, the NHMRC, the Royal College of Pathologists of Australasia and the Victorian Cancer Biobank.

Supplementary material

10549_2010_941_MOESM1_ESM.doc (179 kb)
Supplementary material 1 (DOC 179 kb)
10549_2010_941_MOESM2_ESM.doc (4.3 mb)
Fig. S1 (A) Invasive carcinoma with weak nuclear and cytoplasmic pan-ERβ staining, (B) Invasive carcinoma with strong nuclear and cytoplasmic pan-ERβ staining. (C) Invasive carcinoma with weak nuclear and cytoplasmic ERβ1 staining, (D) Invasive carcinoma with strong nuclear and cytoplasmic ERβ1 staining, (E) Invasive carcinoma with weak nuclear and cytoplasmic ERβ2 staining, (F) Invasive carcinoma with strong nuclear and cytoplasmic ERβ2 staining. Supplementary material 1 (DOC 4436 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Max Yan
    • 1
    Email author
  • Mukta Rayoo
    • 1
  • Elena A. Takano
    • 1
  • kConFab Investigators
    • 2
  • Stephen B. Fox
    • 1
  1. 1.Department of PathologyPeter MacCallum Cancer CentreEast MelbourneAustralia
  2. 2.Peter MacCallum Cancer CentreEast MelbourneAustralia

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