Clinical and molecular predictors of sustained response to trastuzumab in metastatic breast cancer

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Abstract
500 Background: Trastuzumab based chemotherapy has dramatically altered the progression of metastatic breast cancer for patients with HER2/neu positive disease. However, not all patients will have significant response to trastuzumab based chemotherapy. Clinical and molecular predictors are needed to determine who will respond to trastuzumab based chemotherapy. Methods: Patients who received trastuzumab chemotherapy were identified from the BC Cancer Agency Pharmacy Database. Clinical factors were assessed from chart review and database extraction. Immunohistochemical (IHC) analysis was performed using tissue microarray (TMA), and we currently have EGFR, ER status, p53, and MIB-1 stained. We are going to be looking at PTEN, AKT, PR, HER3,and IGF-R as well. Outcomes were defined as sustained response (SR) or no response (NR) Logistic regression analyses were used to evaluate predictive significance of various clinical and IHC factors in outcome. Spearman correlation coefficients were used to determine correlations between factors. Results: We currently have clinical outcome information on 222 patients, and 114 patients with samples suitable for TMA analysis. SR are similar to NR in terms of factors such as disease free interval, estrogen receptor status, age, number of previous lines of chemotherapy and hormonal therapy, and presence or absence of visceral metastases. Patients with grade 2 tumours that were HER2 positive had significantly more sustained responses (45/67, 67%) than those who had grade 3 tumours (64/139, 46%) (p<0.05). We are currently preparing and analyzing tissue by microarray, and this will be presented at ASCO. On the first 75 patients, we have found no significant correlation between EGFR, ER, p53, and MIB-1 with outcome. Patients with positive p53 staining also were more likely to stain for MIB-1. Conclusions: Pathologic grade 2, HER2 positive tumors may have more sustained responses to trastuzumab based treatment than grade 3 tumors. Results on immunohistochemical profiling of 150 tumors treated with trastuzumab will be presented at the ASCO annual meeting. No significant financial relationships to disclose.

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