BC can lose HER2-expression as a result of the selective pressure elicited by HER2-directed therapies61 or, in case of HR-positive/HER2-negative mBC, BC cells can upregulate HER2 expression as a mechanism of resistance to endocrine agents, converting into HER2-positive tumors.62 Therefore, rebiopsy and retest for pathology biomarkers on progressing lesions, including HER2, are crucial for some patients showing treatment resistance or a different disease trajectory, to capture potential heterogeneity and phenotype switch.63 This evidence concerns the gene ERBB2 and breast cancer.