| Title |
TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, December 2011
|
| DOI | 10.1007/s10549-011-1896-1 |
| Pubmed ID | |
| Authors |
Pernille Braemer Hertel, Dongsheng Tu, Bent Ejlertsen, Maj-Britt Jensen, Eva Balslev, Shan Jiang, Frances P. O’Malley, Kathleen I. Pritchard, Lois E. Shepherd, Annette Bartels, Nils Brünner, Torsten O. Nielsen |
| Abstract |
HER2 amplification, TOP2A aberrations, and absence of tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline-containing adjuvant chemotherapy, and this study was undertaken to validate these findings in a similar, but independent, randomized clinical trial. TIMP-1 was examined by immunohistochemistry in archival tumor tissue from 403 of 716 premenopausal high-risk patients with known HER2 and TOP2A status who were randomized to cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF) in the MA.5 trial. Ninety-eight (24%) patients had no TIMP-1 staining of tumor cells, 27% were HER2 amplified, and 18% were TOP2A aberrant. Forty-four percentage was classified as HT responsive (HER2 amplified and/or TIMP-1 negative) and 37% as 2T responsive (TOP2A aberrant and/or TIMP-1 negative). There was no heterogeneity in treatment effect of CEF versus CMF according to TIMP-1. In HT-responsive patients, CEF was superior to CMF with an improved RFS (adjusted HR, 0.64; 95% CI, 0.42-0.97), but this was not significant for OS (adjusted HR, 0.66; 95% CI, 0.42-1.04). A significant HT profile versus treatment interaction was detected for OS (P = 0.03). In 2T-responsive patients, CEF seemed to improve RFS compared to CMF (adjusted HR, 0.67; 95% CI, 0.43-1.03) and improved OS (adjusted HR, 0.58; 95% CI, 0.36-0.93). A significant 2T profile versus treatment interaction was detected for OS (P = 0.01). With this study, we validate a more substantial reduction in mortality by CEF compared to CMF in patients with an HT- or 2T-responsive profile; however, we could not show a similarly significant reduction in RFS events, where a benefit of CEF over CMF was found irrespective of TIMP-1 status. Further studies are necessary before the HT and 2T profiles may be used to direct the use of anthracyclines. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 18% |
| Other | 5 | 13% |
| Student > Master | 4 | 10% |
| Student > Bachelor | 3 | 8% |
| Professor | 2 | 5% |
| Other | 7 | 18% |
| Unknown | 11 | 28% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 15 | 38% |
| Agricultural and Biological Sciences | 4 | 10% |
| Nursing and Health Professions | 3 | 8% |
| Psychology | 2 | 5% |
| Sports and Recreations | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 13 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 December 2011.
All research outputs
#18,301,870
of 22,659,164 outputs
Outputs from Breast Cancer Research and Treatment
#3,678
of 4,612 outputs
Outputs of similar age
#195,562
of 240,792 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#50
of 57 outputs
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