Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer
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Male breast cancer (MBC) is a poorly characterized disease because of its rarity. Clinical management is based on results obtained from randomized trials conducted in women notwithstanding data in the literature suggesting relevant gender-associated differences in terms of biological and clinical behavior. However, a genome-wide characterization of MBC on a transcriptional level is lacking. In this study, gene expression profiles of 37 estrogen receptor positive (ER+) MBC specimens were compared to that of 53 ER+ Female Breast Cancer (FBC) samples similar for clinical and patho-biological features. Almost 1000 genes were found differentially expressed (FDR < 1%) between female and male patients and biological interpretation highlighted a gender-associated modulation of key biological processes ranging from energy metabolism to regulation of translation and matrix remodeling as well as immune system recruitment. Moreover, an analysis of genes correlated to steroid receptors and ERBB2 suggested a prominent role for the androgen receptor in MBC with a minor relevance for progesterone receptor and ERBB2, although, similarly to FBC, a genomic amplification could be observed. Our findings support the idea that breast cancer is a quite different disease in male and female patients and the underlying gender-related biological differences are likely to have clinical implications connected with different susceptibility to treatment.
KeywordsMale breast cancer Gene expression profile Gender differences Breast cancer Pathway analysis
Supported in part by Associazione Italiana per la Ricerca sul Cancro (PIs, MA Pierotti and MG Daidone), Progetto Integrato Oncologia from the Italian Health Ministry (PI, MG Daidone), Alleanza Contro il Cancro (PI, MG Daidone).
Conflict of interest statement
The authors declared that they have no competing interests.
- 6.Curigliano G, Colleoni M, Renne G, Mazzarol G, Gennari R, Peruzzotti G, de Braud E, Robertson C, Maiorano E, Veronesi P, Nole F, Mandala M, Ferretti G, Viale G, Goldhirsch A (2002) Recognizing features that are dissimilar in male and female breast cancer: expression of p21Waf1 and p27Kip1 using an immunohistochemical assay. Ann Oncol 13:895–902PubMedCrossRefGoogle Scholar
- 12.Cappelletti V, Gariboldi M, De Cecco L, Toffanin S, Reid JF, Lusa L, Bajetta E, Celio L, Greco M, Fabbri A, Pierotti MA, Daidone MG (2008) Patterns and changes in gene expression following neo-adjuvant anti-estrogen treatment in estrogen receptor-positive breast cancer. Endocr Relat Cancer 15:439–449PubMedCrossRefGoogle Scholar
- 34.Helleman J, Jansen MP, Ruigrok-Ritstier K, van Staveren IL, Look MP, Meijer-van Gelder ME, Sieuwerts AM, Klijn JG, Sleijfer S, Foekens JA, Berns EM (2008) Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response. Clin Cancer Res 14:5555–5564PubMedCrossRefGoogle Scholar
- 40.Rody A, Holtrich U, Pusztai L, Liedtke C, Gaetje R, Ruckhaeberle E, Solbach C, Hanker L, Ahr A, Metzler D, Engels K, Karn T, Kaufmann M (2009) T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers. Breast Cancer Res 11:R15PubMedCrossRefGoogle Scholar
- 45.Lengyel E, Prechtel D, Resau JH, Gauger K, Welk A, Lindemann K, Salanti G, Richter T, Knudsen B, Vande Woude GF, Harbeck N (2005) C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu. Int J Cancer 113:678–682PubMedCrossRefGoogle Scholar
- 54.Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, Bartlett JMS, Gelmon K, Nahleh Z, Bergh J, Cutuli B, Pruneri G, McCaskill-Stevens W, Gralow J, Hortobagyi G, Cardoso F (2010) Multidisciplinary meeting on male breast cancer: summary and research recommendations. J Clin Oncol 28:2114–2122PubMedCrossRefGoogle Scholar