Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer.
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.
Sørlie
Therese
T
Department of Medicine, Section of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway.
Perou
Charles M
CM
Fan
Cheng
C
Geisler
Stephanie
S
Aas
Turid
T
Nobel
Andrew
A
Anker
Gun
G
Akslen
Lars A
LA
Botstein
David
D
Børresen-Dale
Anne-Lise
AL
Lønning
Per Eystein
PE
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
D000903:Antibiotics, Antineoplastic; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D004317:Doxorubicin; D005472:Fluorouracil