Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease

655 Background: HER-2 overexpression, a predictive marker of tumor aggressiveness and responsiveness to therapy, occurs in 20–30% of breast cancer. Although breast cancer is a heterogeneous disease, HER-2 evaluation is done in primary tumor. HER-2 was measured in both primary and metastases to evaluate whether heterogeneity between primary breast cancer and metastatic sites exists in HER-2 overexpression and the effect of HER-2 on treatment decisions. Methods: Biopsies from primary breast cancer and corresponding metastases of 58 patients were studied. HER-2 overexpression was evaluated immunohistochemically (IHC) in all primary and metastatic sites using CB11 monoclonal antibody and DAKO Hercept-Test scoring. Positive results were confirmed by fluorescence in situ hybridization (FISH). Results: Median time from primary tumor to diagnosis of metastases was 4.5 years (range 1–12 years). Discordance in HER-2 overexpression between primary and metastatic sites was 14% (8 of 58 patients). In 1 patient (2%), HER-2 was negative in metastasis but positive in primary. In 7 (12%) patients HER-2 was positive in metastases and negative in primary. Concordance in HER-2 in primary and metastatic sites was found in 50 (86%) of patients (95% CI: 70.6–94.4). Three patients with HER-2 positive in metastatic sites and negative in primary responded to trastuzumab therapy. Conclusions: HER-2 is an important predictive biological marker for treatment of breast cancer. Possible discordance of HER-2 overexpression between primary and metastatic sites should be considered when making treatment decisions of metastatic sites. No significant financial relationships to disclose.