Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding klotho beta, KLB, when comparing primary tumors of the breast to the ... [Show full abstract] tissue of origin, the normal breast. KLB mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of KLB in primary tumors of the breast was correlated with distant metastasis-free survival in patients with HER2+ subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by PAM50 molecular subtype. KLB may be of relevance to initiation, maintenance or progression of cancers of the female breast.