Breast cancer survival and in vitro tumor response in the extreme drug resistance assay

Purpose. To determine whether in vitro extreme drug resistance (EDR) assay results for patients with breast carcinoma were associated with clinical ou tcome after chemotherapy. Patients and methods. EDR assays were performed on tumor tissue obtained fr om 103 newly diagnosed breast cancer cases. EDR scores of 2 for low, 1 for intermediate, or 0 for extreme drug resistance were determined for each age nt tested. In vitro EDR scores for 4-hydroxycyclophosphamide (4HC) and doxo rubicin were summed for patients treated with AC, or for 4HC and 5-FU for p atients treated with CMF. Treatment selection was blinded to assay results. Results. Median time to progression was significantly shorter for patients with extreme or intermediate in vitro resistance (n = 55, 48 months), compa red to patients with low in vitro resistance, (n = 41, 100 months, p = 0.02 2). Patients demonstrating extreme to intermediate drug resistance also sho wed poorer survival than the low resistance group (49.5 months vs. not reac hed, median follow-up 48 months, p = 0.011). Summed EDR scores, stage, and number of lymph nodes were significantly associated with survival in univar iate and multivariate analysis. Compared to EDR scores of 4, summed EDR sco res of 0-1 and summed EDR scores of 2-3 were associated with a relative ris k of death of 3.09 (95%, CI 1.05-9.06, Cox proportional hazards model, p = 0.040) and 2.35 (95%, CI 1.07-5.15, Cox proportional hazards model, p = 0.0 33), respectively. Conclusion. Extreme drug resistance testing identified patients with indivi dual patterns of drug resistance prior to therapy. In this cohort of breast cancer patients treated with chemotherapy, summed EDR scores were signific antly associated with time to tumor progression and overall survival. EDR r esults may offer a method for optimizing treatment selection.