Overview of meta-analysis of signatures in cancer. We have performed a large-scale meta-analysis of cancer signatures, including 351 publicly available cancer signatures (Additional file 1: Table S1) and 31 breast cancer test datasets (Additional file 1: Table S2). Based on the predictive performance of each signature in 31 breast cancer test datasets and 9 ER-negative (ER-) subsets, we first identified our top 37 signature candidates (Additional file 1: Table S3) for breast cancer prognosis prediction and one signature for prognosis prediction in ER- subsets (Table 4). Using 37,000 random signature permutation tests and 22 verified test datasets, we narrowed down our top 37 candidates to our top three signatures (Table 1). Next, the top three signatures were further evaluated by uni-/multi-variate hazard ratio tests (Table 2) and breast cancer subsets (Table 3), and two of the three were confirmed as valid and independent prognostic signatures. Finally, we examined the ability of the top two signatures to predict chemotherapy outcomes in breast cancer patients (Table 5) and taxane-anthracycline sensitivity in patients with HER2 - beast cancer (Table 6).