title: Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer.
abstract: Neoadjuvant treatment offers an opportunity to correlate molecular variables to treatment response and to explore mechanisms of drug resistance in vivo. Here, we present a statistical analysis of large-scale gene expression patterns and their relationship to response following neoadjuvant chemotherapy in locally advanced breast cancers. We analyzed cDNA expression data from 81 tumors from two patient series, one treated with doxorubicin alone (51) and the other treated with 5-fluorouracil and mitomycin (30), and both were previously studied for correlations between TP53 status and response to therapy. We observed a low frequency of progressive disease within the luminal A subtype from both series (2 of 36 versus 13 of 45 patients; P = 0.0089) and a high frequency of progressive disease among patients with luminal B type tumors treated with doxorubicin (5 of 8 patients; P = 0.0078); however, aside from these two observations, no other consistent associations between response to chemotherapy and tumor subtype were observed. These specific associations could possibly be explained by covariance with TP53 mutation status, which also correlated with tumor subtype. Using supervised analysis, we could not uncover a gene profile that could reliably (>70% accuracy and specificity) predict response to either treatment regimen.
authors.affiliation: Department of Medicine, Section of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway.
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Stephanie
authors.initials: S
authors.lastname: Geisler
authors.forename: Turid
authors.initials: T
authors.lastname: Aas
authors.forename: Andrew
authors.initials: A
authors.lastname: Nobel
authors.forename: Gun
authors.initials: G
authors.lastname: Anker
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: David
authors.initials: D
authors.lastname: Botstein
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D004317:Doxorubicin; D005472:Fluorouracil