Breast Cancer Research and Treatment

, Volume 130, Issue 2, pp 457–463 | Cite as

Alpha- and beta-adrenergic receptor (AR) protein expression is associated with poor clinical outcome in breast cancer: an immunohistochemical study

  • D. G. PoweEmail author
  • M. J. Voss
  • H. O. Habashy
  • K. S. Zänker
  • A. R. Green
  • I. O. Ellis
  • F. Entschladen
Preclinical study


Breast cancer mortality is frequently associated with metastatic disease. Metastasis models have shown adrenoceptor (AR) stimulation induces cell migration which is inhibited by adrenoceptor antagonist drugs. We investigated adrenoceptor protein expression in clinical breast tumours and its association with disease progression and prognosis. Immunohistochemistry on tissue microarrays was used to characterise α1b, α2c and β22 adrenoceptor protein expression in operable breast tumours. Associations with tumour-relevant biological markers and clinical outcome were statistically assessed. Strong α1b expression occurred in large high grade (P < 0.0001), HER2+ (P < 0.0001) or basal-like (CK5/6, P = 0.0005; CK14, P = 0.0001; EGFR, P = 0.003) cancers, showing increased proliferation (Mib1, P = 0.002), decreased apoptosis (Bcl2, P < 0.0001) and poor NPI membership (P = 0.001). α1b expression correlated with poor cancer-specific survival (LR = 7.628, P = 0.022) and tumour recurrence (LR = 6.128, P = 0.047). Strong α2c was over-expressed in high grade (P = 0.007), HER3+ (P = 0.002) and HER4+ (P < 0.0001) cancers with borderline increase in EGFR, p53 and MIB1 proteins, and inverse association with hormonal (PgR, P = 0.002) phenotype. In contrast, strong β2 expression occurred in small-size, luminal-like (ER+, P < 0.001) tumours of low grade (P < 0.001) and lymph node stage (P = 0.027) that showed poor prognosis when hormonal treatment was withheld. Adrenoceptors were not found to be independent predictors of clinical outcome. Alpha1b and α2c AR is over-expressed in basal-like breast tumours of poor prognosis. Strong β2 adrenoceptor expression is seen in patients with a luminal (ER+) tumour phenotype and good prognosis, due to benefits derived from hormonal therapy. These findings suggest a possible role for targeted therapy using adrenoceptor antagonists.


Breast cancer Adrenergic receptor Adrenoceptor Adrenergic antagonist Prognosis, treatment 



Androgen receptor/adrenoceptor


Breast cancer-specific survival




Disease-free interval


Distant metastasis




Oestrogen receptor


Epidermal growth factor receptor




Progesterone receptor



Members of the Institute of Immunology, Witten/Herdecke University were supported by the Fritz Bender Foundation (Munich, Germany). In addition, the ministry of higher education (Egypt) is thanked for funding HOH.

Conflict interests

The authors have no conflict of interests to declare

Supplementary material

10549_2011_1371_MOESM1_ESM.doc (46 kb)
Table 1 Supplementary material 1 (DOC 45 kb)
10549_2011_1371_MOESM2_ESM.doc (81 kb)
Table 2 Characteristics for patients investigated for α1b adrenoceptor protein expression (DOC 90 kb)
10549_2011_1371_MOESM3_ESM.doc (101 kb)
Table 3 Associations between α1b adrenoceptor protein expression and tumour relevant markers (DOC 122 kb)
10549_2011_1371_MOESM4_ESM.doc (81 kb)
Table 4 Characteristics for patients investigated for α2c adrenoceptor protein expression (DOC 90 kb)
10549_2011_1371_MOESM5_ESM.doc (101 kb)
Table 5 Associations between α2c adrenoceptor protein expression and tumour relevant markers (DOC 121 kb)
10549_2011_1371_MOESM6_ESM.doc (80 kb)
Table 6 Characteristics for patients investigated for β2 adrenoceptor protein expression (DOC 90 kb)
10549_2011_1371_MOESM7_ESM.doc (102 kb)
Table 7 Associations between β2 adrenoceptor protein expression and tumour relevant markers (DOC 122 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • D. G. Powe
    • 1
    Email author
  • M. J. Voss
    • 2
  • H. O. Habashy
    • 1
  • K. S. Zänker
    • 2
  • A. R. Green
    • 1
  • I. O. Ellis
    • 1
  • F. Entschladen
    • 2
  1. 1.Department of Cellular Pathology, Queen’s Medical CentreNottingham University Hospitals Trust and School of Molecular Medical Sciences, University of NottinghamNottinghamUK
  2. 2.Institute of ImmunologyUniversity of Witten/HerdeckeWittenGermany

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