Figure 2.

HER2 heterogeneity in breast cancer and implications for HER2-targeted therapies. Approximately 60% of HER2-positive breast cancer is homogeneous regarding HER2 status in invasive tumor cells (left) and 40% shows HER2 intratumoral heterogeneity either with genetic heterogeneity or non-genetic heterogeneity (right). Breast cancer patients with HER2 homogeneous status have a higher chance of reaching pCR, longer event-free survival and distant recurrence-free survival. The treatment regimens can be further tuned by other factors. Neoadjuvant anti-HER2 targeted therapy combined with chemotherapy can be applied in ER-negative cases, while anti-HER2 targeted therapy alone may be sufficient for HER2-enriched and PIK3CA wild-type cases. Breast cancer patients with HER2 ITH are less likely to reach pCR and develop distant metastases. Escalated treatments with anti-HER2 targeted therapy combined with chemotherapy should be applied from the beginning of the treatment to improve clinical outcomes in this group of patients.