ABSTRACT
PURPOSE: An in vitro adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was designed to require only a limited number of cells and shorten test turnaround time with a high success rate. This study investigated the correlation between in vitro doxorubicin sensitivity of tumor cells and early systemic recurrence, defined as recurrence within 2 years after surgery. METHODS: From January 2004 to March 2007, the ATP-CRA for doxorubicin was tested in 128 patients among breast cancer patients treated at Gangnam Severance Hospital, Seoul, Korea. The American Joint Committee on Cancer stages for all patients were II and III. All patients received doxorubicin-based chemotherapy. Selected patients were divided into a chemosensitive group and a non-chemosensitive group, according to a 40% cell death rate as a cut-off value. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with breast cancer. RESULTS: The mean age of the patients investigated was 44.6-years-old, the mean follow-up period was 39.9 months, and recurrence free survival was 38.6 months. Thirteen recurrences were observed during follow-up. Among 13 patients with a recurrence, eight had a recurrence within 2 years (early recurrence). All of the early recurring patients belonged to the non-sensitive group. Doxorubicin sensitivity results measured by ATP-CRA were related with early recurrence free survival in patients with breast cancer (p=0.030). The mean cell death rate derived from the ATP-CRA for the early recurrence group tended to be lower than that of the non-early recurrence group, but the difference was not statistically significant (p=0.05). CONCLUSION: Doxorubicin sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence against doxorubicin-based adjuvant chemotherapy in patients with breast cancer.
Subject(s)
Mortality , Breast NeoplasmsABSTRACT
PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.