SA02 Trial: A Genomics-Based Prospective Study of Adjuvant Chemotherapy in Node-Positive Early Breast Cancer with «Good-Prognosis Signature».
Authors: B. Francois, E. Jean Marc, F. Jean Marc, B. Thomas, T. Xavier, C. Tarpin, T. Agnes, J. Jocelyne, L. Eric, E. Benjamin, O. Isabelle, M. Agnes, V. Patrice
Journal: Cancer Research (2009)

Abstract Background: Adjuvant chemotherapy (CT) for node-positive (N+) early breast cancer (EBC) is based upon an anthracycline-taxane combination. However, the benefit of taxane is limited to a small population, but associated to morbid and financial costs, making crucial the identification of patients likely to benefit or not from anthracycline-based regimen without taxane. Using DNA microarrays to profile a retrospective series of 498 patients (pts) treated with adjuvant anthracycline-based CT without taxane, we identified and validated a gene expression signature (GES) associated with metastatic relapse. The corresponding Relapse Score (RS) sorted the pts in two groups: the “good-prognosis” group (75% of pts) with a 5-year metastasis-free survival (MFS) of 82%, and the “poor-prognosis” group (25% of pts) with a 56% 5-year MFS. A prospective multicentric cohort of 220 pts, SA02, was initiated to analyze anthracycline-based adjuvant CT without taxane in N+ EBC patients with a “good-prognosis” RS, with the aim of confirming their good prognosis.Methods: Women with surgical EBC were screened for inclusion in 4 French hospitals. After diagnosis of node positivity, frozen samples were used for hybridizationon Affymetrix U133 Plus 2.0 microarrays. “Good-prognosis” pts were included in the SA02 cohort and received 6 FEC100 cycles (Fluoro-uracile 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2, every 21 days), followed by adjuvant radiotherapy, hormone therapy and/or trastuzumab according to standard guidelines. Pts with a “poor-prognosis” RS were not included in the cohort.Results: Between April 2007 and May 2009, samples from 106 eligible N+ EBC pts were collected for gene profiling. The profiling failed for 34 samples (32%), due to insufficient RNA amount (6%), poor RNA quality (17%), or technical problems (9%). Sixty-six pts (92%) were defined as “good-prognosis” and enrolled in the SA02 cohort, while only 2 pts (3%) were defined as “poor-prognosis”; 4 pts could not be assigned a prognostic group. The percentage of “good-prognosis” RS was higher than observed in the identification and validation retrospective series. Comparison of histo-clinical data between these retrospective series and the 72 samples successfully profiled in the present study showed more favourable features in the current series, with fewer positive lymph nodes, lower grade, more HR-positive and less ERBB2-positive tumors. After a median follow-up of 1 year, no relapse or death was observed in the SA02 cohort.Conclusion: This interim analysis confirms that genomic analyses are feasible in clinical practice, even if more challenging than in a retrospective academic environment. A shift in histo-clinical features of N+ EBC was observed between the retrospective series and the current prospective series; this could be due to the evolution of EBC diagnostic methods and treatment strategies. Study is ongoing, and final follow-up data will be available in 2014. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4041.