title: Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy.
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 individualised 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 this with the corresponding performance when 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 (OR)=6.5 (95% confidence interval (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 receiver operating characteristics (ROC) curve were 0.78 and 0.79, respectively. The ORs 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.
authors.affiliation: Department of Oncology, Institute of Medical Sciences, University Hospital, Lund, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Niméus-Malmström
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ritz
authors.forename: Patrik
authors.initials: P
authors.lastname: Edén
authors.forename: Anders
authors.initials: A
authors.lastname: Johnsson
authors.forename: Mattias
authors.initials: M
authors.lastname: Ohlsson
authors.forename: Carina
authors.initials: C
authors.lastname: Strand
authors.forename: Görel
authors.initials: G
authors.lastname: Ostberg
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
authors.forename: Carsten
authors.initials: C
authors.lastname: Peterson
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D011237:Predictive Value of Tests; D017697:Premenopause; D012313:RNA / Q000235:genetics; D012372:ROC Curve
chemical_list: D018076:DNA, Complementary; D012313:RNA; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate