Figure 7. Nuclear HER4 predicts poorer trastuzumab response and is an adverse prognostic marker in HER2 positive breast cancer patients.

(A & B) TMAs containing paraffin embedded breast tumours from a well-annotated HER2 positive breast cancer patients were stained for HER4 expression by IHC. Patients were split into two groups according to the positive and negative cytoplasmic and nuclear HER4 staining as defined in the methods section. The relapse-free survival and overall survival of the two groups were plotted in Kaplan-Meier curves according to the cytoplasmic and nuclear HER4 staining in breast cancer patients (n=73). (C) A schematic diagram shows a window of opportunity study conducted among HER2 positive breast cancer patients who received trastuzumab monotherapy followed by neoadjuvant chemotherapy with trastuzumab before surgery. Tumour specimens were collected at the baseline, 21 days after trastuzumab monotherapy and at the final stage after completed 4 cycles of neoadjuvant docetaxel chemotherapy 100 mg/m² with 6mg/kg trastuzumab. (D) Nuclear HER4 expression was analysed using IHC in paired tissue samples (baseline and at 21 days) from 5 patients who received one dose of trastuzumab monotherapy. The differences in HER4 IRS scores between the pairs were asssesed by paired t-test (* indicates p<0.05). (E) Nuclear HER4 expression at day 21 was correlated with the ratios of tumour volumes and Ki67 stainings (between day 21 and baseline) using linear regression (upper panels). The table below shows the HER4 scorings of the individual 5 patients with their respective tumour volume and Ki67 ratios.