title: Response prediction to neoadjuvant chemotherapy: comparison between pre-therapeutic gene expression profiles and in vitro chemosensitivity assay.
abstract: Although the use of (neo-)adjuvant chemotherapy in breast cancer patients has resulted in improved outcome, not all patients benefit equally. We have evaluated the utility of an in vitro chemosensitivity assay in predicting response to neoadjuvant chemotherapy. Pre-therapeutic biopsies were obtained from 30 breast cancer patients assigned to neoadjuvant epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (Epi/Doc) in a prospectively randomized clinical trial. Biopsies were subjected to a standardized ATP-based Epi/Doc chemosensitivity assay, and to gene expression profiling. Patients then received 3 cycles of chemotherapy, and response was evaluated by changes in tumor diameter and Ki67 expression. The efficacy of Epi/Doc in vitro was correlated with differential changes in tumor cell proliferation in response to Epi/Doc in vivo (p = 0.0011; r = 0.73670, Spearmańs rho), but did not predict for changes in tumor size. While a pre-therapeutic gene expression signature identified tumors with a clinical response to Epi/Doc, no such signature could be found for tumors that responded to Epi/Doc in vitro, or tumors in which Epi/Doc exerted an antiproliferative effect in vivo. This is the first prospective clinical trial to demonstrate the utility of a standardized in vitro chemosensitivity assay in predicting the individual biological response to chemotherapy in breast cancer.
authors.affiliation: Department of Gynecology and Obstetrics and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. christian.singer@meduniwien.ac.at
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Florian
authors.initials: F
authors.lastname: Klinglmüller
authors.forename: Rembert
authors.initials: R
authors.lastname: Stratmann
authors.forename: Christine
authors.initials: C
authors.lastname: Staudigl
authors.forename: Anneliese
authors.initials: A
authors.lastname: Fink-Retter
authors.forename: Daphne
authors.initials: D
authors.lastname: Gschwantler
authors.forename: Samir
authors.initials: S
authors.lastname: Helmy
authors.forename: Georg
authors.initials: G
authors.lastname: Pfeiler
authors.forename: Anne Catharina
authors.initials: AC
authors.lastname: Dressler
authors.forename: Christian
authors.initials: C
authors.lastname: Sartori
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin