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 Journal Article

  

Authors:	Rincon, M.; Broadwater, G.; Harris, L.; Crocker, A.; Weaver, D.; Dressler, L.; Berry, D.; Sutton, L.; Michaelson, R.; Messino, M.; Kirshner, J.; Fleming, G.; Winer, E.; Hudis, C.; Appel, S.; Norton, L.; Muss, H.
Article 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/m2 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. © 2006 Springer Science+Business Media, LLC.
Keywords:	immunohistochemistry; adult; cancer survival; controlled study; human tissue; protein expression; treatment outcome; treatment response; aged; middle aged; major clinical study; cancer growth; paclitaxel; breast cancer; antineoplastic agents, phytogenic; genetic transcription; cancer cell culture; in vitro study; breast neoplasms; time factors; kaplan-meiers estimate; neoplasm metastasis; interleukin 6; interleukin-6; multivariate analysis; metastases; breast metastasis; drug sensitivity; multidrug resistance; p-glycoprotein; sample; glycoprotein p; multidrug resistance protein 1; il-6; paclitaxel response; pgp
Journal Title:	Breast Cancer Research and Treatment
Volume:	100
Issue:	3
ISSN:	0167-6806
Publisher:	Springer
Date Published:	2006-12-01
Start Page:	301
End Page:	308
Language:	English
DOI:	10.1007/s10549-006-9251-7
PUBMED:	16773437
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33750728891&partnerID=40&md5=2c6425b22f45eac8f0f7a73c62bb7fe1
Notes:	--- - "Cited By (since 1996): 8" - "Export Date: 4 June 2012" - "CODEN: BCTRD" - "Source: Scopus"

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