Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy (CMF)

Emma Niméus-Malmström, Cecilia Ritz, Patrik Edén, Anders Johnsson, Mattias Ohlsson, Carina Strand, Görel Östberg, Mårten Fernö and Carsten Peterson
Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy
European Journal of Cancer 42, 2729-2737 (2006)

Abstract:
A large proportion of breast cancer patients are treated with adjuvant chemotherapy after the primary operation, but some will recur in spite of this treatment. In order to achieve an improved and more individualized therapy, our knowledge in mechanisms for drug resistance needs to be increased. We have investigated to what extent cDNA microarray measurements could distinguish the likelihood of recurrences after adjuvant CMF (cyclophosphamide, methotrexate and 5-fluorouracil) treatment of premenopausal, lymph node positive breast cancer patients, and have also compared with the corresponding performance using conventional clinical variables.
We tried several gene selection strategies, and built classifiers using the resulting gene lists. The best performing classifier with odds ratio=6.5 (95% CI=1.4-62) did not outperform corresponding classifiers based on clinical variables. For the clinical variables, calibrated on the samples, either using all the clinical parameters or the Nottingham Prognostic Index (NPI) parameters, the areas under the ROC curve were 0.78 and 0.79, respectively. The odds ratios at 90% sensitivity were 15 (95% CI=3.1-140) and 10 (95% CI=2.1-97), respectively. Our data have provided evidence for a comparable prediction of clinical outcome in CMF-treated breast cancer patients using conventional clinical variables and gene expression based markers.

LU TP 04-46