Skip to main content

Advertisement

Springer Nature Link
Log in

Androgen receptor expression is a predictive marker in chemotherapy-treated patients with endocrine receptor-positive primary breast cancers

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The androgen receptor (AR) is intensively discussed as a prognostic and/or predictive marker in breast cancer patients.

Methods

We evaluated the value of AR mRNA expression with the Affymetrix HG-U 133A array in 3 different cohorts: a cohort of breast cancer patients who received adjuvant treatment (cohort A; n = 165), a cohort of untreated breast cancer patients (cohort B; n = 200) and a cohort of chemotherapy-treated breast cancer patients with estrogen receptor (ER)-positive tumors (cohort C; n = 223).

Results

AR mRNA expression was associated with lower grading (Grades 1 and 2) as well as ER and progesterone receptor (PgR) positivity in all cohorts. In the treated cohort (cohort A), low androgen receptor expression was associated with shorter event-free survival (OR 2,34, 95 % CI 1.01–5.43, p = 0.047) which was not seen in the untreated cohort B. Subgroup analysis revealed that shorter survival of patients with low AR mRNA expression was observed mainly in the ER-positive subgroup of patients treated with adjuvant chemotherapy. In the validation cohort C we could confirm a benefit of chemotherapy for the group of tumors with high AR mRNA expression (5-year event-free survival (EFS) 74 % versus 57 %, p = 0.013). In this cohort, low AR mRNA expression was associated with shorter event-free survival also in multivariate analysis (OR 2.86, 95 % CI 1.29–6.35, p = 0.010) adjusted for HER2, ki-67, tumor size, age and tumor grade.

Conclusions

We provide evidence that AR expression is associated with chemotherapy responsiveness in ER-positive patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ (2003) Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 120:725–731

    Article  PubMed  CAS  Google Scholar 

  • Castellano I, Allia E, Accortanzo V, Vandone AM, Chiusa L, Arisio R, Durando A, Donadio M, Bussolati G, Coates AS, Viale G, Sapino A (2010) Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Res Treat 124:607–617

    Article  PubMed  CAS  Google Scholar 

  • Chintamani Kulshreshtha P, Chakraborty A, Singh L, Mishra AK, Bhatnagar D, Saxena S (2010) Androgen receptor status predicts response to chemotherapy, not risk of breast cancer in Indian women. World J Surg Oncol 8:64

    Article  PubMed  CAS  Google Scholar 

  • Collins LC, Cole KS, Marotti JD, Hu R, Schnitt SJ, Tamimi RM (2011) Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses’ health study. Mod Pathol 24:924–931

    Article  PubMed  Google Scholar 

  • Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13:983–992

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez LO, Corte MD, Vazquez J, Junquera S, Sanchez R, Alvarez AC, Rodriguez JC, Lamelas ML, Vizoso FJ (2008) Androgen receptor expression in breast cancer: relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitors. BMC Cancer 8:149

    Article  PubMed  Google Scholar 

  • Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, Carey M, Agarwal R, Meric-Berstam F, Traina TA, Hudis C, Hortobagyi GN, Gerald WL, Mills GB, Hennessy BT (2009) Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 15:2472–2478

    Article  PubMed  CAS  Google Scholar 

  • Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, Marotti JD, Hankinson SE, Colditz GA, Tamimi RM (2011) Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res 17:1867–1874

    Article  PubMed  CAS  Google Scholar 

  • Karn T, Metzler D, Ruckhaberle E, Hanker L, Gatje R, Solbach C, Ahr A, Schmidt M, Holtrich U, Kaufmann M, Rody A (2010) Data-driven derivation of cutoffs from a pool of 3,030 Affymetrix arrays to stratify distinct clinical types of breast cancer. Breast Cancer Res Treat 120:567–579

    Article  PubMed  Google Scholar 

  • Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JG, Henzen-Logmans SC (1996) The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer 32A:1560–1565

    Article  PubMed  CAS  Google Scholar 

  • Liao DJ, Dickson RB (2002) Roles of androgens in the development, growth, and carcinogenesis of the mammary gland. J Steroid Biochem Mol Biol 80:175–189

    Article  PubMed  CAS  Google Scholar 

  • Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI and de Bono JS (2012) Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol 13(12):1210–1217. doi:10.1016/S1470-2045(12)70473-4

    Google Scholar 

  • Loibl S, Muller BM, von Minckwitz G, Schwabe M, Roller M, Darb-Esfahani S, Ataseven B, du Bois A, Fissler-Eckhoff A, Gerber B, Kulmer U, Alles JU, Mehta K, Denkert C (2011) Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy. Breast Cancer Res Treat 130:477–487

    Article  PubMed  CAS  Google Scholar 

  • Lundin KB, Henningson M, Hietala M, Ingvar C, Rose C, Jernstrom H (2011) Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients. Br J Cancer 105:1676–1683

    Article  PubMed  CAS  Google Scholar 

  • Macedo LF, Guo Z, Tilghman SL, Sabnis GJ, Qiu Y, Brodie A (2006) Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res 66:7775–7782

    Article  PubMed  CAS  Google Scholar 

  • McNamara KM, Yoda T, Takagi K, Miki Y, Suzuki T, Sasano H (2012) Androgen receptor in triple negative breast cancer. J Steroid Biochem Mol Biol 133C:66–76

    Google Scholar 

  • Naderi A, Chia KM, Liu J (2011) Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptor-negative breast cancer. Breast Cancer Res 13:R36

    Article  PubMed  CAS  Google Scholar 

  • Ogawa Y, Hai E, Matsumoto K, Ikeda K, Tokunaga S, Nagahara H, Sakurai K, Inoue T, Nishiguchi Y (2008) Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers. Int J Clin Oncol 13:431–435

    Article  PubMed  CAS  Google Scholar 

  • Park S, Koo JS, Kim MS, Park HS, Lee JS, Kim SI, Park BW, Lee KS (2011) Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol 22:1755–1762

    Article  PubMed  CAS  Google Scholar 

  • Park S, Park HS, Koo JS, Yang WI, Kim SI, Park BW (2012) Higher expression of androgen receptor is a significant predictor for better endocrine-responsiveness in estrogen receptor-positive breast cancers. Breast Cancer Res Treat 133:311–320

    Article  PubMed  CAS  Google Scholar 

  • Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, Jindal S, Segara D, Jia L, Moore NL, Henshall SM, Birrell SN, Coetzee GA, Sutherland RL, Butler LM, Tilley WD (2009) Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Cancer Res 69:6131–6140

    Article  PubMed  CAS  Google Scholar 

  • Peters KM, Edwards SL, Nair SS, French JD, Bailey PJ, Salkield K, Stein S, Wagner S, Francis GD, Clark SJ, Brown MA (2012) Androgen receptor expression predicts breast cancer survival: the role of genetic and epigenetic events. BMC Cancer 12:132

    Article  PubMed  CAS  Google Scholar 

  • Rabiau N, Dechelotte P, Adjakly M, Kemeny JL, Guy L, Boiteux JP, Kwiatkowski F, Bignon YJ, Bernard-Gallon D (2011) BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: correlation between RT-qPCR and immunohistochemical detection. Oncol Rep 26:695–702

    PubMed  CAS  Google Scholar 

  • Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32

    Article  PubMed  CAS  Google Scholar 

  • Ryan CJ, Tindall DJ (2011) Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. J Clin Oncol 29:3651–3658

    Article  PubMed  CAS  Google Scholar 

  • Yeh S, Hu YC, Wang PH, Xie C, Xu Q, Tsai MY, Dong Z, Wang RS, Lee TH, Chang C (2003) Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. J Exp Med 198:1899–1908

    Article  PubMed  CAS  Google Scholar 

  • Yu Q, Niu Y, Liu N, Zhang JZ, Liu TJ, Zhang RJ, Wang SL, Ding XM, Xiao XQ (2011) Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol 22:1288–1294

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gynecology, University Medical Center, Martinistrasse 52, 20246, Hamburg, Germany

    Isabell Witzel, Monika Graeser, Dina Schütze, Alma Rausch, Fritz Jänicke, Karin Milde-Langosch & Volkmar Müller

  2. Department of Obstetrics and Gynecology, University Hospital, Frankfurt, Germany

    Thomas Karn

  3. Department of Obstetrics and Gynecology, University Hospital, Mainz, Germany

    Markus Schmidt

  4. Stratifyer Molecular Oncology GmbH, Cologne, Germany

    Ralph Wirtz

Authors
  1. Isabell Witzel
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Monika Graeser
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Thomas Karn
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Markus Schmidt
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Ralph Wirtz
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Dina Schütze
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Alma Rausch
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Fritz Jänicke
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Karin Milde-Langosch
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Volkmar Müller
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Isabell Witzel.

Additional information

Isabell Witzel and Monika Graeser equally contributed to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Witzel, I., Graeser, M., Karn, T. et al. Androgen receptor expression is a predictive marker in chemotherapy-treated patients with endocrine receptor-positive primary breast cancers. J Cancer Res Clin Oncol 139, 809–816 (2013). https://doi.org/10.1007/s00432-013-1382-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-013-1382-8

Keywords