Breast cancer is a remarkably heterogeneous disease. Different therapeutic agents induce different responses in different patients. Gene expression profiling has shown promise in the neoadjuvant setting as a tool in prediction of treatment response to specific agent(s). Now a new study by investigators at US Oncology and MD Anderson independently validated ChemoFx®, a new Multi-Gene Predictors (MGPs) test developed by Precision Therapeutics. The study showed a potential role of the in vitro chemosensitivity test and multi-gene predictors in determining a patient's likelihood of response to multi-drug chemotherapy regimens in breast cancer. Results of the study were presented at the 2010 December San Antonio Breast Cancer Symposium (SABCS).
Women with stage II/III breast cancer participating in the trial were treated with neoadjuvant chemotherapy consisting of four cycles of fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX). Most HER-2 positive patients also received trastuzumab.
Multi-gene predictors (MGPs) of FEC, TX and docetaxel/fluorouracil/epirubicin/cyclophosphamide (TFEC) sensitivity were developed using vitro chemoresponse (ChemoFx®) microarray gene data from 39 breast cancer cell lines exposed to these drug combinations and publicly-available gene expression data for the same cell lines. MGPs were not developed for treatment with trastuzumab. Area under the receiver-operator curve (AUC) was used to evaluate the performance of the three MGPs’ to predict patient pathologic complete response (pCR). Patients who did or did not receive trastuzumab were evaluated separately. Validation was performed blindly and the predictors were applied without knowledge of patient clinical outcome (n=68).
The conclusion of the study, conducted between Precision Therapeutics, US Oncology, and MD Anderson Cancer Center, was that in this blinded validation study, cell line-derived MGPs of multi-drug chemotherapy regimens showed promising performance, particularly among patient with ER-negative breast cancers.
The prediction accuracies were low for patients who received trastuzumab together with chemotherapy (n=25), indicating that the MGPs may have be regimen-specific.
"This data is critical to the advancement of research in personalized medicine and for improvements in cancer therapy," says Dr. Holly Gallion, Vice President of Clinical Affairs at Precision. "Because so few patients respond to any given round of chemotherapy, histology alone cannot tell us which patients will respond. When used with ChemoFx®, MGPs may have the capacity to accurately identify responders before treatment, thereby helping to minimize the selection of ineffective therapies for cancer patients, and this is one of the main goals in seeking to improve personalized cancer treatment."
Further clinical data are needed to confirm this finding.
Shen K, Pusztai L, Qi Y, Symmans WF, Song N, Rice SD, Gabrin MJ, O'Shaughnessy JA, Holmes FA. Multi-Gene Predictors Developed from Breast Cancer Cell Lines To Predict Response to Chemotherapy: A Validation Study on US Oncology Study 02-103. [P2-09-39] San Antonio Breast Cancer Symposium (SABCS). Poster Session 2: Prognostic and Predictive Factors: Response Predictions - Biomarkers and Other Factors (7:00 AM-9:00 AM)