Topoisomerase II alpha protein and responsiveness of breastn cancer to adjuvant chemotherapy with CEF compared to CMF in the NCIC CTG randomized MA.5 adjuvant trial
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : F. P. O’Malley S. Chia D. Tu L. E. Shepherd M. N. Levine D. Huntsman V. H. Bramwell I. L. Andrulis K. I. Pritchard
- چاپ و سال / کشور: 2011
Description
Overexpression of topoisomerase II protein (topo 2a) is postulated to be more closely associated with responsiveness to anthracycline-containing chemotherapy than human epidermal growth factor receptor type 2 (HER2) gene amplification or alterations in the topoisomerase II alpha gene (TOP2A). The authors used tissue microarrays from 477 of 710 premenopausal women with node-positive breast cancer randomized to CEF or CMF adjuvant chemotherapy in the NCIC Clinical Trials Group Mammary 5 (MA.5) trial. No significant interaction was found between treatment and continuous topo 2a level in either relapse-free (RFS) or overall survival (OS). In 136 patients (28.5%) whose tumors showed topo 2a overexpression by immunohistochemistry based on a cut-off of 13%, CEF was superior to CMF for RFS (adjusted HR 0.45; 95% CI 0.25–0.82; P = 0.009) and OS (adjusted HR 0.50; 95% CI 0.26–0.96; P = 0.04). When tumors lacked topo 2a overexpression, CEF was not superior for RFS (adjusted HR 0.88; 95% CI 0.64–1.22; P = 0.46) or OS (adjusted HR 0.95; 95% CI 0.66–1.38; P = 0.80). Interaction between topo 2a and treatment was borderline significant for RFS (P = 0.04) and OS (P = 0.05) and not substantially more significant than between TOP2A gene alteration (Pinteraction = 0.09 for RFS and 0.02 for OS) or HER2 overexpression (Pinteraction = 0.002 for RFS and 0.009 for OS). Topo 2a protein overexpression based on the cut-off identified in this study, TOP2A gene alterations and HER2 protein overexpression were each associated with responsiveness to anthracyclinecontaining chemotherapy. The topo 2a protein analysis was exploratory and will require further validation.
Breast Cancer Res Treat (2011) 128:401–409 DOI 10.1007/s10549-011-1511-5 Received: 12 November 2010 / Accepted: 6 April 2011 / Published online: 26 April 2011 Springer Science+Business Media, LLC. 2011
