Moreover, the tumor microenvironment cannot be reproduced in two-dimensional cell culture, individualized therapy screening is labor-intensive and representation of certain breast cancer subtypes, such as HER2-enriched, claudin-low, and normal-like, is restrained by the lack of an accurate breast cancer cell line options, increasing the challenge to address characterization and therapeutic strategies in vitro and call upon alternative models for such purposes [88, 89]. Here, ERBB2 is linked to breast cancer.