title: Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in human breast cancers.
abstract: Collagen gel droplet embedded culture-drug sensitivity test (CD-DST) is the newly developed in vitro chemosensitivity test that has several advantages over the conventional ones. The aim of the present study is to examine the clinical usefulness of this test in the prediction of response to chemotherapy in breast cancer patients. Seventy patients with primary (n = 45) or locally recurrent (n = 25) breast cancers were recruited, and each patient underwent tumor biopsy before chemotherapy. The biopsy specimens were used for CD-DST and immunohistological examination of 6 biological markers (P-gp, erbB2, p53, BCL2, MIB1 and ER-alpha). As chemotherapy, cyclophosphamide 600 mg/m(2) plus epirubicin 60 mg/m(2) q3w (CE, n = 28) or docetaxel 60 mg/m(2) q3w (DOC, n = 42) was given. Interpretable results using the CD-DST assay were obtained from 84.3% (59/70) of tumor specimens studied. Of the 18 tumors diagnosed as CE sensitive by CD-DST, 15 (83.3%) exhibited a response to CE therapy and none of the 5 tumors diagnosed as CE resistant by CD-DST exhibited a response to CE therapy. Of the 14 tumors diagnosed as DOC sensitive by CD-DST, 13 (92.9%) exhibited a response to DOC therapy and only one of the 22 tumors diagnosed as DOC resistant by CD-DST exhibited a response to DOC therapy. P-gp expression was found to exhibit a significant (p < 0.05) association with the resistance to CE therapy but not to DOC therapy. Diagnostic accuracy (72.7%) achieved by P-gp was lower than that (87.0%) achieved by CD-DST in CE therapy. Expressions of other biological markers (erbB2, p53, BCL2, MIB1 and ER-alpha) were not significantly associated with response to CE or DOC therapy. These results demonstrate that CD-DST can predict the response to CE and DOC therapy with a high accuracy in breast cancer patients and seems to be superior to the conventional predictors.
authors.affiliation: Department of Surgical Oncology, Osaka University Medical School, Yamada-oka, Suita, Osaka, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takamura
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Motomura
authors.forename: Hideo
authors.initials: H
authors.lastname: Inaji
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003094:Collagen; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005782:Gels; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D043823:Taxoids
chemical_list: D014408:Biomarkers, Tumor; D005782:Gels; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D003094:Collagen; D017239:Paclitaxel