title: Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response.
abstract: Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group.
authors.affiliation: Department of Obstetrics and Gynecology, J.W. Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. achim.rody@em.uni-frankfurt.de
authors.forename: A
authors.initials: A
authors.lastname: Rody
authors.forename: T
authors.initials: T
authors.lastname: Karn
authors.forename: R
authors.initials: R
authors.lastname: Gätje
authors.forename: A
authors.initials: A
authors.lastname: Ahr
authors.forename: C
authors.initials: C
authors.lastname: Solbach
authors.forename: K
authors.initials: K
authors.lastname: Kourtis
authors.forename: M
authors.initials: M
authors.lastname: Munnes
authors.forename: S
authors.initials: S
authors.lastname: Loibl
authors.forename: S
authors.initials: S
authors.lastname: Kissler
authors.forename: E
authors.initials: E
authors.lastname: Ruckhäberle
authors.forename: U
authors.initials: U
authors.lastname: Holtrich
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: M
authors.initials: M
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D043823:Taxoids / Q000008:administration & dosage; D016875:tau Proteins / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D043823:Taxoids; D016875:tau Proteins; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II