The role of androgen receptors for new therapeutic strategies and the prognostic outcome in patients with breast cancer


The role of androgen receptors for new therapeutic strategies and the prognostic outcome in patients with breast cancer

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Title: The role of androgen receptors for new therapeutic strategies and the prognostic outcome in patients with breast cancer
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Article_Title: The role of androgen receptors for new therapeutic strategies and the prognostic outcome in patients with breast cancer
Authors: Diana Narita, George-Ciprian Pribac, Aurel Ardelean
Affiliation: 1 University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
2 ”Vasile Goldis” Western University Arad, Romania
Abstract: It has been suggested that AR could be prognostic markers for breast cancers but their role in
the pathogenesis of breast carcinomas is far to be clear. The purpose of this study was to asses by
immunohistochemistry the AR expression in female breast carcinomas and to correlate the results with the immunoexpression ER/PR status, HER2/neu status and some histopathological features of carcinomas, like histological type and grade, nodal and metastasis status. We have found a positive correlation between AR and the histological type of the tumor and the grade of differentiation, most of AR-positive carcinomas being well and moderate differentiated. A negative association was found between AR and the nodal status, the majorities of AR-positive cases being lymph node negative. We did not find a statistical significant correlation with HER2, ER/PR and metastasis status. We can conclude that AR could be useful for establishing new therapeutic strategies and for evaluating the prognostic outcome in patients with breast cancer.
Keywords: breast cancer, estrogen receptors, progesterone receptors, androgen receptors, HER2/neu
References: Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogeninduced
mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J 2000; 14, pp. 1725-1730.
Dimitrakakis C, Zhou J, Bondy CA. Androgens and mammary growth and neoplasia. Fertil Steril
2002; 77:S26-S33.
Sauter ER, Tichansky DS, Chervoneva I, Diamandis EP. Circulating testosterone and prostatespecific
antigen in nipple aspirate fluid and tissue are associated with breast cancer. Environ Health Perspect 2002; 110, pp. 241-246.
Hackenberg R and Schultz KD. Androgen receptor mediated growth control of breast cancer and
endometrial cancer modulated by antiandrogenand androgen-like steroids. J Steroid Biochem
Mol Biol 1996; 56, pp. 113-117.
Somboonporn W and Davis S. Testosterone effects on the breast: implications for testosterone therapy
for women. Endocrine Reviews 2004; 25, pp. 374-388.
Berrino F, Micheli A. Serum hormone levels after menopause and subsequent breast cancer. J Natl
Cancer Inst 1996; 88, pp. 291-296.
Zeleniuch-Jacquotte A, Bruning PF, Bonfrer JMG, Koenig KL, Shore RE, Kim MY, Pasternack BS, Toniolo P. Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women. Am J Epidemiol 1997; 145, pp. 1030-1038.
Zeleniuch-Jacquotte A, Shore RE, Koenig KL, Akhmedkhanov A, Afanasyeva Y, Kato I, Kim MY, Rinaldi S, Kaaks R, Toniolo P. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer 2004; 90, pp. 153-159.
Thomas HV, Key TJ, Allen DS, Moor JW, Dowsett M., Fentiman IS, Wang DY. A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer 1997; 76, pp. 401-405.
Suter NM, Malone KE, Daling JR, Doody DR and Ostrander EA. Androgen Receptor (CAG)n and (GGC)n Polymorphisms and Breast Cancer Risk in a Population-Based Case-Control Study
of Young Women. Cancer Epidemiol Biomarkers Prev 2003;12, pp. 127-135.
Birrell SN, Hall RE, Tilley WD. Role of androgen receptor in human breast cancer. J Mammary
Gland Neoplasia 1998; 3, pp. 95-103.
Ortmann J, Prifti S, Bohlmann MK, Rehberger- Schneider S, Strowitzki T, Rabe T. Testosterone
and 5α-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Gynecol Endocrinol 2002; 16, pp. 113-120.
Birrell SN, Bemtel JM, Hickey TE, Ricciardelli C, Weger MA, Horsfall DJ, Tilley WD. Androgens
induce divergent proliferative responses in human breast cancer cell lines. J Steroid Biochem Mol Biol 1995; 52, pp. 459-467.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;
19, pp. 403-410.
Ellis I O, Dowsett M, Bartlett J, Walker R, Cooke T. Recommendations for HER2 testing in the UK.
J Clin Pathol 2000; 53, pp. 890-892.
Ellis LM, Wittliff L, Bryant MS. Correlation of estrogen, progesterone and androgen receptors
in breast cancer. Am J Surg 1989;157, pp. 57-581.
Kuenen-Boumeester V, Van Der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JGM, and Henzen-Logmans SC. The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer 1996; 32A, pp. 1560-1565.
Kimura N, Mizokami A, Oonuma T, Sasano H, and Nagura H. Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. J Histochem Cytochem 1993; 41, pp. 671-678.
Bieche I, Parfait B, Tozlu S, Lidereau R, Vidaud M. Quantitation of androgen receptor gene
expression in sporadic breast tumors by realtime RT-PCR: evidence that MYC is an ARregulated gene. Carcinogenesis 2001; 22, pp. 1521-1526.
Isola JJ. Immunohistochemical demonstration of androgen receptor in breast cancer and its
relationship to other prognostic factors. J Pathol 1993;170, pp. 31-35.
Agoff SN, Swanson PE, Linden H. Androgen receptor expression in estrogen receptor-negative breast
cancer. Immunohistochemical, clinical and prognostic associations. Am J Clin Pathol 2003; 120, pp. 725-731.
Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora Ratschek M, Tavassoli FA, Denk
H. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new
therapeutic strategie. Cancer 2003; 98, pp. 703-710.
Leal C, Henrique R, Monteiro P, Lopes C, Bento MJ, De Sousa CP, Lopes P, Olson S, Silva MD, Page DL. Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers. Hum Pathol 2001; 32, pp. 487-493.
Selim A, El-Ayat G and Wells CA. Androgen receptor expression in ductal carcinoma in situ of the
breast: relation to oestrogen and progesterone receptors. J Clin Pathol 2002; 55, pp. 14-16.
Bayer-Garner IB, Smoller B. Androgen receptors: a marker of increase sensitivity for identifying
breast cancer in skin metastasis of unknown primary site. Mod Pathol 2000; 13, pp. 119-122.
Narita D, Raica M, Anghel A, Suciu C, Cîmpean AM. Immunohistochemical localization of prostatespecific antigen in benign and malignant breast conditions. Rom J Morphol and Embryol 2005;
46, pp. 41-45.
Read_full_article: pdf/18-2008/SU08Narita.pdf
Correspondence: Diana Narita, Department of Biochemistry, University of Medicine and Pharmacy „Victor
Babes” Timisoara, email: diana_narita@yahoo.com

Read full article
Article Title: The role of androgen receptors for new therapeutic strategies and the prognostic outcome in patients with breast cancer
Authors: Diana Narita, George-Ciprian Pribac, Aurel Ardelean
Affiliation: 1 University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania
2 ”Vasile Goldis” Western University Arad, Romania
Abstract: It has been suggested that AR could be prognostic markers for breast cancers but their role in
the pathogenesis of breast carcinomas is far to be clear. The purpose of this study was to asses by
immunohistochemistry the AR expression in female breast carcinomas and to correlate the results with the immunoexpression ER/PR status, HER2/neu status and some histopathological features of carcinomas, like histological type and grade, nodal and metastasis status. We have found a positive correlation between AR and the histological type of the tumor and the grade of differentiation, most of AR-positive carcinomas being well and moderate differentiated. A negative association was found between AR and the nodal status, the majorities of AR-positive cases being lymph node negative. We did not find a statistical significant correlation with HER2, ER/PR and metastasis status. We can conclude that AR could be useful for establishing new therapeutic strategies and for evaluating the prognostic outcome in patients with breast cancer.
Keywords: breast cancer, estrogen receptors, progesterone receptors, androgen receptors, HER2/neu
References: Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA. Testosterone inhibits estrogeninduced
mammary epithelial proliferation and suppresses estrogen receptor expression. FASEB J 2000; 14, pp. 1725-1730.
Dimitrakakis C, Zhou J, Bondy CA. Androgens and mammary growth and neoplasia. Fertil Steril
2002; 77:S26-S33.
Sauter ER, Tichansky DS, Chervoneva I, Diamandis EP. Circulating testosterone and prostatespecific
antigen in nipple aspirate fluid and tissue are associated with breast cancer. Environ Health Perspect 2002; 110, pp. 241-246.
Hackenberg R and Schultz KD. Androgen receptor mediated growth control of breast cancer and
endometrial cancer modulated by antiandrogenand androgen-like steroids. J Steroid Biochem
Mol Biol 1996; 56, pp. 113-117.
Somboonporn W and Davis S. Testosterone effects on the breast: implications for testosterone therapy
for women. Endocrine Reviews 2004; 25, pp. 374-388.
Berrino F, Micheli A. Serum hormone levels after menopause and subsequent breast cancer. J Natl
Cancer Inst 1996; 88, pp. 291-296.
Zeleniuch-Jacquotte A, Bruning PF, Bonfrer JMG, Koenig KL, Shore RE, Kim MY, Pasternack BS, Toniolo P. Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women. Am J Epidemiol 1997; 145, pp. 1030-1038.
Zeleniuch-Jacquotte A, Shore RE, Koenig KL, Akhmedkhanov A, Afanasyeva Y, Kato I, Kim MY, Rinaldi S, Kaaks R, Toniolo P. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer 2004; 90, pp. 153-159.
Thomas HV, Key TJ, Allen DS, Moor JW, Dowsett M., Fentiman IS, Wang DY. A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer 1997; 76, pp. 401-405.
Suter NM, Malone KE, Daling JR, Doody DR and Ostrander EA. Androgen Receptor (CAG)n and (GGC)n Polymorphisms and Breast Cancer Risk in a Population-Based Case-Control Study
of Young Women. Cancer Epidemiol Biomarkers Prev 2003;12, pp. 127-135.
Birrell SN, Hall RE, Tilley WD. Role of androgen receptor in human breast cancer. J Mammary
Gland Neoplasia 1998; 3, pp. 95-103.
Ortmann J, Prifti S, Bohlmann MK, Rehberger- Schneider S, Strowitzki T, Rabe T. Testosterone
and 5α-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Gynecol Endocrinol 2002; 16, pp. 113-120.
Birrell SN, Bemtel JM, Hickey TE, Ricciardelli C, Weger MA, Horsfall DJ, Tilley WD. Androgens
induce divergent proliferative responses in human breast cancer cell lines. J Steroid Biochem Mol Biol 1995; 52, pp. 459-467.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;
19, pp. 403-410.
Ellis I O, Dowsett M, Bartlett J, Walker R, Cooke T. Recommendations for HER2 testing in the UK.
J Clin Pathol 2000; 53, pp. 890-892.
Ellis LM, Wittliff L, Bryant MS. Correlation of estrogen, progesterone and androgen receptors
in breast cancer. Am J Surg 1989;157, pp. 57-581.
Kuenen-Boumeester V, Van Der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JGM, and Henzen-Logmans SC. The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer 1996; 32A, pp. 1560-1565.
Kimura N, Mizokami A, Oonuma T, Sasano H, and Nagura H. Immunocytochemical localization of androgen receptor with polyclonal antibody in paraffin-embedded human tissues. J Histochem Cytochem 1993; 41, pp. 671-678.
Bieche I, Parfait B, Tozlu S, Lidereau R, Vidaud M. Quantitation of androgen receptor gene
expression in sporadic breast tumors by realtime RT-PCR: evidence that MYC is an ARregulated gene. Carcinogenesis 2001; 22, pp. 1521-1526.
Isola JJ. Immunohistochemical demonstration of androgen receptor in breast cancer and its
relationship to other prognostic factors. J Pathol 1993;170, pp. 31-35.
Agoff SN, Swanson PE, Linden H. Androgen receptor expression in estrogen receptor-negative breast
cancer. Immunohistochemical, clinical and prognostic associations. Am J Clin Pathol 2003; 120, pp. 725-731.
Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora Ratschek M, Tavassoli FA, Denk
H. Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new
therapeutic strategie. Cancer 2003; 98, pp. 703-710.
Leal C, Henrique R, Monteiro P, Lopes C, Bento MJ, De Sousa CP, Lopes P, Olson S, Silva MD, Page DL. Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers. Hum Pathol 2001; 32, pp. 487-493.
Selim A, El-Ayat G and Wells CA. Androgen receptor expression in ductal carcinoma in situ of the
breast: relation to oestrogen and progesterone receptors. J Clin Pathol 2002; 55, pp. 14-16.
Bayer-Garner IB, Smoller B. Androgen receptors: a marker of increase sensitivity for identifying
breast cancer in skin metastasis of unknown primary site. Mod Pathol 2000; 13, pp. 119-122.
Narita D, Raica M, Anghel A, Suciu C, Cîmpean AM. Immunohistochemical localization of prostatespecific antigen in benign and malignant breast conditions. Rom J Morphol and Embryol 2005;
46, pp. 41-45.
*Correspondence: Diana Narita, Department of Biochemistry, University of Medicine and Pharmacy „Victor
Babes” Timisoara, email: diana_narita@yahoo.com