Androgen pathway dysregulation in BRCA1-mutated breast tumors

• Published in: Breast cancer research and treatment 2003-05, Vol.79 (1), p.121-127
• Main Authors: BERNS, Els M. J. J, DIRKZWAGER-KIEL, Maaike J. M, KUENEN-BOUMEESTER, Vibeke, TIMMERMANS, Mieke, VERHOOG, Leon C, VAN DEN OUWELAND, Ans M. W, MEIJER-HEIJBOER, Hanne, KLIJN, Jan G. M, VAN DER KWAST, Theo H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer research; Cancer therapies; Genes, BRCA1; Genes, BRCA2; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Mammary gland diseases; Matched-Pair Analysis; Medical sciences; Middle Aged; Mutation; Receptors, Androgen - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Receptors, Steroid - metabolism; Tumor Suppressor Protein p53 - metabolism; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1023/A:1023347409599

Using array analysis for screening RNA from BRCA1-mutated and sporadic breast tumors, we observed that AIGF/FGF-8 expression was lost in BRCA1-mutated breast tumors. Since this growth factor is induced by androgens, we studied the androgen receptor (AR) expression in BRCA-mutated tumors and in matched sporadic breast tumors. Paraffin embedded breast tumors of carriers of a BRCA1 mutation (n=41, median age of patients at time of surgery was 41 years [range 28-59 years]) or a BRCA2 mutation (n=14, median age 41 years [range 31-85 years]) were analyzed for the presence of ER-alpha, PR, P53 and AR using standard immunohistochemical techniques. All statistical tests used, Pearson chi2 and Fisher exact, were two-sided. The AR was only present in 12% of BRCA1-mutated tumors, with mutations located at the C-terminal half of the BRCA1-gene. The AR expression was significantly more prevalent, however, in a series of 61 sporadic breast tumors (80%) and in BRCA2-mutated tumors (50%). In contrast to an increased percentage of p53 positive cells, in 66% of the BRCA1-mutated tumors, the ER-alpha expression was observed only in 25% and the PR in 13% of these specimens. The three steroid hormone receptors were expressed in about half of the BRCA2-mutated specimens studied. Our data add to the emerging evidence that the biological phenotype of BRCA1-associated tumors may be different from BRCA2 and non-hereditary cases. The loss of the AR expression, as shown by immunohistochemistry, together with the observed loss of other steroid hormone receptors in BRCA1-mutated tumors may lead to a hormone-independent growth or to anti-hormone resistant growth of these tumors.