• What is AR?
  • AR in Breast Cancer
  • Clinical Trials

AR

The androgen receptor (AR) plays a role in the pathogenesis of prostate cancer and can be expressed in invasive breast cancer (Itkonen and Mills 2012; Gonzalez et al 2008). AR is the product of the AR gene, which is located on the X chromosome. AR is in the nuclear receptor superfamily and is part of the steroid receptor family, and it has a six-region structure with a defined functional domain (Itkonen and Mills 2012).

Amplification of the AR gene and AR mutations occur in 30% and 1-30% of castration-resistant prostate cancer, respectively (Waltering et al. 2012). AR expression is measured using immunohistochemistry (IHC), and is detectable in the majority of castration-resistant prostate cancer (Linja et al. 2001; Waltering et al. 2012) and 75% of invasive breast cancers (Collins et al. 2011; Gonzalez et al 2008).

Related Pathways

Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2016. AR. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/ar/?tab=0 (Updated September 12).

Last Updated: September 12, 2016

AR in Breast Cancer

Androgen receptor (AR) expression is detectable in 75% of breast cancers (Collins et al. 2011; Gonzalez et al 2008). AR mutations are not known to be important in breast cancer.

Gene or Protein Invasive Breast Cancer Hormone Receptor Positive (ER+ and/or PR+) Invasive Breast Cancer HER2-positive Invasive Breast Cancer Triple-negative Invasive Breast Cancer
AR expression 75% (Collins et al. 2011; Gonzalez et al 2008) 90% (References in Secreto et al. 2012) 44% (Arslan et al. 2012) ≤ 50% (McNamara et al. 2013; Mrklić et al. 2012)
NOTE: AR = androgen receptor; ER = estrogen receptor; PR = progesterone receptor

Testing for AR Expression in Breast Cancer

In contrast with ER and PR expression in breast cancer, standard practice guidelines have not been established for measuring AR expression and defining AR status. Even so, retrospective studies demonstrate that AR status may have prognostic implications in some types of breast cancer (Hu et al. 2011). There are preliminary data that AR status may be predictive of benefit with an androgen receptor antagonist (Ayca Gucalp et al. 2013).

Several different immunohistochemistry (IHC) cutoff levels have been used to define AR status in breast tumors (Table 2). Another approach is to calculate IHC scores ranging from 0 to 3 to define AR status as positive or negative (Gonzalez et al. 2008; Ren et al. 2013). Other studies follow the protocol established for prostate cancer, which involves an immune-reactivity scoring system combining several measures for AR protein levels (Loibl et al. 2011).


Table 2. AR Immunohistochemistry Test Interpretations Across Studies.
Percentage Of Cells That Are Immunoreactive AR Status (Reference)
>60 Highly positive (Secreto et al. 2012)
>30–60 Moderately positive (Secreto et al. 2012)
>50 High (Ogawa et al. 2008)
>10 Positive (Ayca Gucalp et al. 2013; Collins et al. 2011; Hu et al. 2011)
≥10 Positive (Moinfar et al. 2003; Park et al. 2010; Niemeier et al. 2010; Micello et al. 2010)
10–50 Intermediate (Ogawa et al. 2008)
≥1–30 Poorly positive (Secreto et al. 2012)
≥1 Positive (Mrklić et al. 2012; Sutton et al. 2012)
1–10 Low positive (Collins et al. 2011; Hu et al. 2011)
<10 Low (Ogawa et al. 2008)
<10 Negative (Moinfar et al. 2003; Park et al. 2010; Niemeier et al. 2010; Micello et al. 2010; Ayca Gucalp et al. 2012)
0 Negative (Collins et al. 2011; Hu et al. 2011)
0 None (Ogawa et al. 2008)
0 Absent (Secreto et al. 2012)
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Contributors: Justin M. Balko, Pharm. D., Ph.D., Ingrid A. Mayer, M.D., M.S.C.I., Mia Levy, M.D., Ph.D., Carlos L. Arteaga, M.D.

Suggested Citation: Balko, J., I. Mayer, M. Levy, C. Arteaga. 2014. AR in Breast Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/breast-cancer/ar/ (Updated March 31).

Last Updated: March 31, 2014

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