Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients

Jenny C. Chang, Eric C. Wooten, Anna Tsimelzon, Susan G. Hilsenbeck, M. Carolina Gutierrez, Yee Lu Tham, Mamta Kalidas, Richard M Elledge, Syed Mohsin, C. Kent Osborne, Gary C. Chamness, D. Craig Allred, Michael T. Lewis, Helen Wong, Peter O'Connell

Research output: Contribution to journalArticle

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Abstract

Purpose: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. Patients and Methods: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m2 every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 μg was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). Results: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G2M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. Conclusion: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.

Original languageEnglish (US)
Pages (from-to)1169-1177
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number6
DOIs
StatePublished - Feb 20 2005
Externally publishedYes

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docetaxel
Gene Expression Profiling
Breast Neoplasms
Residual Neoplasm
Gene Expression
Drug Therapy
Therapeutics
Laser Capture Microdissection
Biopsy
Cyclins
Neoadjuvant Therapy
Sirolimus
Cell Cycle Checkpoints
Oligonucleotide Array Sequence Analysis
Neoplasms
RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chang, J. C., Wooten, E. C., Tsimelzon, A., Hilsenbeck, S. G., Gutierrez, M. C., Tham, Y. L., ... O'Connell, P. (2005). Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. Journal of Clinical Oncology, 23(6), 1169-1177. https://doi.org/10.1200/JCO.2005.03.156

Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. / Chang, Jenny C.; Wooten, Eric C.; Tsimelzon, Anna; Hilsenbeck, Susan G.; Gutierrez, M. Carolina; Tham, Yee Lu; Kalidas, Mamta; Elledge, Richard M; Mohsin, Syed; Osborne, C. Kent; Chamness, Gary C.; Allred, D. Craig; Lewis, Michael T.; Wong, Helen; O'Connell, Peter.

In: Journal of Clinical Oncology, Vol. 23, No. 6, 20.02.2005, p. 1169-1177.

Research output: Contribution to journalArticle

Chang, JC, Wooten, EC, Tsimelzon, A, Hilsenbeck, SG, Gutierrez, MC, Tham, YL, Kalidas, M, Elledge, RM, Mohsin, S, Osborne, CK, Chamness, GC, Allred, DC, Lewis, MT, Wong, H & O'Connell, P 2005, 'Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients', Journal of Clinical Oncology, vol. 23, no. 6, pp. 1169-1177. https://doi.org/10.1200/JCO.2005.03.156
Chang, Jenny C. ; Wooten, Eric C. ; Tsimelzon, Anna ; Hilsenbeck, Susan G. ; Gutierrez, M. Carolina ; Tham, Yee Lu ; Kalidas, Mamta ; Elledge, Richard M ; Mohsin, Syed ; Osborne, C. Kent ; Chamness, Gary C. ; Allred, D. Craig ; Lewis, Michael T. ; Wong, Helen ; O'Connell, Peter. / Patterns of resistance and incomplete response to docetaxel by gene expression profiling in breast cancer patients. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 6. pp. 1169-1177.
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abstract = "Purpose: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. Patients and Methods: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m2 every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 μg was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). Results: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G2M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. Conclusion: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.",
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AU - Chang, Jenny C.

AU - Wooten, Eric C.

AU - Tsimelzon, Anna

AU - Hilsenbeck, Susan G.

AU - Gutierrez, M. Carolina

AU - Tham, Yee Lu

AU - Kalidas, Mamta

AU - Elledge, Richard M

AU - Mohsin, Syed

AU - Osborne, C. Kent

AU - Chamness, Gary C.

AU - Allred, D. Craig

AU - Lewis, Michael T.

AU - Wong, Helen

AU - O'Connell, Peter

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N2 - Purpose: Chemotherapy for operable breast cancer decreases the risk of death. Docetaxel is one of the most active agents in breast cancer, but resistance or incomplete response is frequent. Patients and Methods: Core biopsies from 24 patients were obtained before treatment with neoadjuvant docetaxel (four cycles, 100 mg/m2 every 3 weeks), and response was assessed after chemotherapy. After 3 months of neoadjuvant chemotherapy, surgical specimens (n = 13) were obtained, and laser capture microdissection (LCM; n = 8) was performed to enrich for tumor cells. From each core, surgical, and LCM specimen, sufficient total RNA (3 to 6 μg was extracted for cDNA array analysis using the Affymetrix HgU95-Av2 GeneChip (Affymetrix, Santa Clara, CA). Results: From the initial core biopsies, differential patterns of expression of 92 genes correlated with docetaxel response (P = .001). However, the molecular patterns of the residual cancers after 3 months of docetaxel treatment were strikingly similar, independent of initial sensitivity or resistance. This relative genetic homogeneity after treatment was observed in both LCM and non-LCM surgical specimens. The residual tumor after treatment in tumors that were initially sensitive indicates selection of a residual and resistant subpopulation of cells. The gene expression pattern was populated by genes involved in cell cycle arrest at G2M (eg, mitotic cyclins and cdc2) and survival pathways involving the mammalian target of rapamycin. Conclusion: A specific and consistent gene expression pattern was found in residual tumors after docetaxel treatment. These profiles provide therapeutic targets that could lead to improved treatment.

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