| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
Predict Response to Anthracycline-based Therapy in Locally Advanced Breast Cancer1
Rush Medical College, Chicago, Illinois 60612 [J. S. C, S. G-B., S. C., H. D. P.]; Cook County Hospital, Chicago, Illinois 60612 [E. M., V. R., G. F.]; and Vysis, Inc, Downers Grove, Illinois 60515 [S. S., K. J.]
Purpose: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase II
gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association.
Experimental Design: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase II and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry.
Results: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase II amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase II amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase II (9 patients) was also associated with favorable response (P = 0.021).
Conclusions: Coamplification of erbB-2 and topoisomerase II is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase II biology.
This article has been cited by other articles:
|
|
 |
|
  D. Rayson, D. Richel, S. Chia, C. Jackisch, S. van der Vegt, and T. Suter Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies Ann. Onc., September 1, 2008; 19(9): 1530 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cardoso, M. Saghatchian, A. Thompson, E. Rutgers, and for the TRANSBIG Consortium Steering Committee Inconsistent Criteria Used in American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer J. Clin. Oncol., April 20, 2008; 26(12): 2058 - 2059. [Full Text] [PDF]
|
|
|
|
 |
|
 L.-P. P. Tran and J. L. Grabinski Chemotherapy for Early-Stage Breast Cancer: A Paradigm in Flux Journal of Pharmacy Practice, February 1, 2008; 21(1): 46 - 56. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Morabito, M. C. Piccirillo, K. Monaco, C. Pacilio, F. Nuzzo, P. Chiodini, C. Gallo, A. de Matteis, F. Perrone, and NCI Naples Breast Cancer Group First-Line Chemotherapy for HER-2 Negative Metastatic Breast Cancer Patients Who Received Anthracyclines as Adjuvant Treatment Oncologist, November 1, 2007; 12(11): 1288 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Jorgensen, K. V. Nielsen, and B. Ejlertsen Pharmacodiagnostics and Targeted Therapies--A Rational Approach for Individualizing Medical Anticancer Therapy in Breast Cancer Oncologist, April 1, 2007; 12(4): 397 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Tretiakova, M Turkyilmaz, T Grushko, M Kocherginsky, C Rubin, B Teh, and X J Yang Topoisomerase II{alpha} in Wilms' tumour: gene alterations and immunoexpression J. Clin. Pathol., December 1, 2006; 59(12): 1272 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tanner, J. Isola, T. Wiklund, B. Erikstein, P. Kellokumpu-Lehtinen, P. Malmstrom, N. Wilking, J. Nilsson, and J. Bergh Topoisomerase II{alpha} Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-Escalated Anthracycline-Based Adjuvant Chemotherapy in HER-2/neu-Amplified Breast Cancer: Scandinavian Breast Group Trial 9401 J. Clin. Oncol., June 1, 2006; 24(16): 2428 - 2436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. U. Buzdar Topoisomerase II{alpha} Gene Amplification and Response to Anthracycline-Containing Adjuvant Chemotherapy in Breast Cancer J. Clin. Oncol., June 1, 2006; 24(16): 2409 - 2411. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Tinari, R. Lattanzio, C. Natoli, E. Cianchetti, D. Angelucci, E. Ricevuto, C. Ficorella, P. Marchetti, S. Alberti, M. Piantelli, et al. Changes of Topoisomerase II{alpha} Expression in Breast Tumors after Neoadjuvant Chemotherapy Predicts Relapse-Free Survival Clin. Cancer Res., March 1, 2006; 12(5): 1501 - 1506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Colozza, E. Azambuja, F. Cardoso, C. Sotiriou, D. Larsimont, and M. J. Piccart Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann. Onc., November 1, 2005; 16(11): 1723 - 1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Knoop, H. Knudsen, E. Balslev, B. B. Rasmussen, J. Overgaard, K. V. Nielsen, A. Schonau, K. Gunnarsdottir, K. E. Olsen, H. Mouridsen, et al. Retrospective Analysis of Topoisomerase IIa Amplifications and Deletions As Predictive Markers in Primary Breast Cancer Patients Randomly Assigned to Cyclophosphamide, Methotrexate, and Fluorouracil or Cyclophosphamide, Epirubicin, and Fluorouracil: Danish Breast Cancer Cooperative Group J. Clin. Oncol., October 20, 2005; 23(30): 7483 - 7490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P J Barrett-Lee Growth factor signalling in clinical breast cancer and its impact on response to conventional therapies: a review of chemotherapy Endocr. Relat. Cancer, July 1, 2005; 12(Supplement_1): S125 - S133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Durbecq, M. Paesmans, F. Cardoso, C. Desmedt, A. Di Leo, S. Chan, K. Friedrichs, T. Pinter, S. Van Belle, E. Murray, et al. Topoisomerase-II{alpha} expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel Mol. Cancer Ther., October 1, 2004; 3(10): 1207 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Ross, J. A. Fletcher, K. J. Bloom, G. P. Linette, J. Stec, W. F. Symmans, L. Pusztai, and G. N. Hortobagyi Targeted Therapy in Breast Cancer: The HER-2/neu Gene and Protein Mol. Cell. Proteomics, April 1, 2004; 3(4): 379 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Giordano Update on Locally Advanced Breast Cancer Oncologist, December 1, 2003; 8(6): 521 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ross, J. A. Fletcher, G. P. Linette, J. Stec, E. Clark, M. Ayers, W. F. Symmans, L. Pusztai, and K. J. Bloom The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy Oncologist, August 1, 2003; 8(4): 307 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Hansel, A. Rahman, M. Hidalgo, P. J. Thuluvath, K. D. Lillemoe, R. Shulick, J.-L. Ku, J.-G. Park, K. Miyazaki, R. Ashfaq, et al. Identification of Novel Cellular Targets in Biliary Tract Cancers Using Global Gene Expression Technology Am. J. Pathol., July 1, 2003; 163(1): 217 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Park and C. D. James Lanthionine Synthetase Components C-like 2 Increases Cellular Sensitivity to Adriamycin by Decreasing the Expression of P-Glycoprotein through a Transcription-mediated Mechanism Cancer Res., February 1, 2003; 63(3): 723 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Climent, J. A. Martinez-Climent, D. Blesa, M. J. Garcia-Barchino, R. Saez, D. Sanchez-Izquierdo, P. Azagra, A. Lluch, and J. Garcia-Conde Genomic Loss of 18p Predicts an Adverse Clinical Outcome in Patients with High-Risk Breast Cancer Clin. Cancer Res., December 1, 2002; 8(12): 3863 - 3869. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
