title: Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806.
abstract: Several reports have suggested that breast cancer patients with elevated serum levels of interleukin-6 (IL-6) have a worse prognosis than patients with lower levels. We have studied IL-6 in breast cancer cell lines and have shown that autocrine production of IL-6 can confer multi-drug resistance in vitro by inducing multidrug resistance gene-1 transcription with subsequent overexpression of P-glycoprotein (PGP). Both IL-6 and PGP expression can be measured in malignant cells using immunohistochemical (IHC) techniques. We hypothesized that patients whose tumors expressed higher amounts of IL-6 or PGP would be less likely to respond to paclitaxel, an agent affected by the PGP pathway. If so, then IL-6 could serve as a predictive factor for paclitaxel sensitivity. Both IL-6 and PGP expression were measured in patients treated in a randomized trial that compared three doses of single agent paclitaxel (175, 210, and 250 mg/m(2) over 3 h every 3 weeks) in 469 women with metastatic breast cancer (CALGB 9342). No difference in complete and partial response was found among the three treatment arms. Tissue blocks in this trial were analyzed for IL-6 (154 patients) and PGP (149 patients) in paraffin-embedded sections from tumor samples; clinical characteristics of these patients were similar to the total sample of 469 patients. There were no significant differences among IL-6 or PGP scores whether measured as continuous or dichotomous variables, or by other scoring, and response to paclitaxel. In multivariate analysis neither IL-6 nor PGP was a significant predictor of time to progression or overall survival. IHC expression of IL-6 and PGP levels in tumor cells is not a predictive marker for response to paclitaxel in women with metastatic breast cancer.
authors.affiliation: Vermont Cancer Center, University of Vermont, Burlington, VT, USA.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Harris
authors.forename: Abigail
authors.initials: A
authors.lastname: Crocker
authors.forename: Donald
authors.initials: D
authors.lastname: Weaver
authors.forename: Lynn
authors.initials: L
authors.lastname: Dressler
authors.forename: Donald
authors.initials: D
authors.lastname: Berry
authors.forename: Linda
authors.initials: L
authors.lastname: Sutton
authors.forename: Richard
authors.initials: R
authors.lastname: Michaelson
authors.forename: Michael
authors.initials: M
authors.lastname: Messino
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kirshner
authors.forename: Gini
authors.initials: G
authors.lastname: Fleming
authors.forename: Eric
authors.initials: E
authors.lastname: Winer
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Stacy
authors.initials: S
authors.lastname: Appel
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Hyman
authors.initials: H
authors.lastname: Muss
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use*; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; C508600:IL6 protein, human; D015850:Interleukin-6; D017239:Paclitaxel