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Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133, Milan, Italy

    Maurizio Callari, Vera Cappelletti, Loris De Cecco, Valeria Musella, Patrizia Miodini, Silvia Veneroni, Manuela Gariboldi & Maria Grazia Daidone

  2. Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Via Adamello 16, 20139, Milan, Italy

    Loris De Cecco & Manuela Gariboldi

  3. Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy

    Marco Alessandro Pierotti

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  1. Maurizio Callari
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  2. Vera Cappelletti
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  3. Loris De Cecco
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  4. Valeria Musella
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  8. Marco Alessandro Pierotti
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  9. Maria Grazia Daidone
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Correspondence to Marco Alessandro Pierotti or Maria Grazia Daidone.

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10549_2010_1015_MOESM6_ESM.jpg

Clustering analysis with PgR associated genes. Using a set of clones differentially expressed between PgR+ and PgR− MBC samples, a hierarchical clustering analysis was performed on the MBC dataset itself (A) as well as on our FBC dataset (B) and on the Chanrion FBC dataset (C) samples. A sub-cluster containing 7/8 PgR− tumors was noticed in the clustering of MBC samples, while a quite random distribution of PgR− tumors was observed in FBC datasets (JPG 111 kb)

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Callari, M., Cappelletti, V., De Cecco, L. et al. Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer. Breast Cancer Res Treat 127, 601–610 (2011). https://doi.org/10.1007/s10549-010-1015-8

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  • DOI: https://doi.org/10.1007/s10549-010-1015-8

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