Metastatic disease itself [33, 38, 53], and increasing number of metastatic sites were also found to be independent adverse prognostic factors for BCBM progression, in both the general BC population (effect estimates range 2.64–28.46 and 1.65–150.858, respectively) [29, 33, 38, 55, 70, 74, 79] and in patients with HER2-positive disease [26, 61]. Here, ERBB2 is linked to breast cancer.