Comparison Of Her2 Extra Cellular Domain (Ecd) Serum Level At The Time Of Metastasis With Her2 Status Modification Between Primary Breast Cancers And Their Respective Metastases

1030 Background: Modification of HER2 level of expression/amplification between primary breast cancer and late metastasis was reported as a rare event. We investigated the usefulness of HER2 ECD serum level assessment at the time of metastasis to identify modification of HER2 status in the metastatic tissue. Methods: We performed a retrospective comparison of HER2 level of expression/amplification on paraffin-embedded tissues from 69 patients of both primary breast cancers and their distant metastasis using immunohistochemistry (IHC) (CB11, Ventana) and chromogenic in situ hybridization (CISH) (Zymed). For 60 patients, frozen serum at time of metastasis was available and HER 2 ECD serum level was measured with an Elisa commercial kit (Oncogene Science); we used 15ng/ml as cut-off value. Results: Among the 69 primary tumors, 9 were HER2 positive, 7 on IHC and 7 on CISH (but 2 of these were only 2+ on IHC). There were 13 metastatic HER2 positive lesions (7 on IHC, 9 on CISH and 3 positive using both methods), resulting in a clinically relevant modification of HER2 status in 8 patients: 6 patients became HER2 positive and 2 patients became HER2 negative on metastatic samples. Among the 60 patients with available frozen serum at the time of metastasis, 16 had elevated HER2 ECD serum level, 7 (54%) of them having a HER2+ metastatic tissue on either IHC or CISH out of the 13 HER2+ metastatic samples whereas in 47 HER2 negative ones, 9 (19%) had an elevated HER2 ECD serum level (p=0.012, Pearson chi-square). Specificity of HER2 ECD serum level was 81% and sensitivity was 54% with a negative predictive value of 86%. Conclusions: In this retrospective series, clinically relevant HER2 status of metastatic tissue was modified in 12% of patients. Elevated HER2 ECD serum level at the time of metastasis was significantly linked with metastatic tissue HER2 overexpression/amplification suggesting its potential utility to select patients for whom metastasis biopsy could change therapeutic strategy. No significant financial relationships to disclose.