Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.<b>Experimental Design:</b> A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data <i>in silico</i> Biomarkers were immunohistochemically assessed in 697 MBCs (<i>n</i> = 477, training; <i>n</i> = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.<b>Results:</b> Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank <i>P</i> = 0.013; HR = 1.77, 1.12-2.8 and <i>P</i> = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (<i>P</i> = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set.
Gene copy number variations (CNVs) analysis showed amplification of PIK3CA in 8.1%, EGFR in 6.8% and CCND1 in 16% of MBCs, whereas deletion of ESR1 was detected in 15% of MBCs.