title: Predicting response to docetaxel neoadjuvant chemotherapy for advanced breast cancers through genome-wide gene expression profiling.
abstract: Neoadjuvant chemotherapy with docetaxel for advanced breast cancer can improve the radicality for a subset of patients, but some patients suffer from severe adverse drug reactions without any benefit. To establish a method for predicting responses to docetaxel, we analyzed gene expression profiles of biopsy materials from 29 advanced breast cancers using a cDNA microarray consisting of 36,864 genes or ESTs, after enrichment of cancer cell population by laser microbeam microdissection. Analyzing eight PR (partial response) patients and twelve patients with SD (stable disease) or PD (progressive disease) response, we identified dozens of genes that were expressed differently between the 'responder (PR)' and 'non-responder (SD or PD)' groups. We further selected the nine 'predictive' genes showing the most significant differences and established a numerical prediction scoring system that clearly separated the responder group from the non-responder group. This system accurately predicted the drug responses of all of nine additional test cases that were reserved from the original 29 cases. Moreover, we developed a quantitative PCR-based prediction system that could be feasible for routine clinical use. Our results suggest that the sensitivity of an advanced breast cancer to the neoadjuvant chemotherapy with docetaxel could be predicted by expression patterns in this set of genes.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, and Department of Breast Surgery, The Cancer Institute Hospital of JFCR, Tokyo 108-8639, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Zembutsu
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Aya
authors.initials: A
authors.lastname: Sasaki
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Minoru
authors.initials: M
authors.lastname: Okazaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D000077143:Docetaxel; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D017698:Postmenopause; D011237:Predictive Value of Tests; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000077143:Docetaxel