TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients

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Standard

TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients. / Hertel, Pernille Bræmer; Tu, Dongsheng; Ejlertsen, Bent Laursen; Jensen, Maj-Britt Raaby; Balslev, Eva; Jiang, Shan; O'Malley, Frances P.; Pritchard, Kathleen I.; Shepherd, Lois E.; Bartels, Annette; Brunner, Nils; Nielsen, Torsten O.

I: Breast Cancer Research and Treatment, Bind 132, Nr. 1, 2012, s. 225-234.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Hertel, PB, Tu, D, Ejlertsen, BL, Jensen, M-BR, Balslev, E, Jiang, S, O'Malley, FP, Pritchard, KI, Shepherd, LE, Bartels, A, Brunner, N & Nielsen, TO 2012, 'TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients', Breast Cancer Research and Treatment, bind 132, nr. 1, s. 225-234. https://doi.org/10.1007/s10549-011-1896-1

APA

Hertel, P. B., Tu, D., Ejlertsen, B. L., Jensen, M-B. R., Balslev, E., Jiang, S., O'Malley, F. P., Pritchard, K. I., Shepherd, L. E., Bartels, A., Brunner, N., & Nielsen, T. O. (2012). TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients. Breast Cancer Research and Treatment, 132(1), 225-234. https://doi.org/10.1007/s10549-011-1896-1

Vancouver

Hertel PB, Tu D, Ejlertsen BL, Jensen M-BR, Balslev E, Jiang S o.a. TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients. Breast Cancer Research and Treatment. 2012;132(1):225-234. https://doi.org/10.1007/s10549-011-1896-1

Author

Hertel, Pernille Bræmer ; Tu, Dongsheng ; Ejlertsen, Bent Laursen ; Jensen, Maj-Britt Raaby ; Balslev, Eva ; Jiang, Shan ; O'Malley, Frances P. ; Pritchard, Kathleen I. ; Shepherd, Lois E. ; Bartels, Annette ; Brunner, Nils ; Nielsen, Torsten O. / TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients. I: Breast Cancer Research and Treatment. 2012 ; Bind 132, Nr. 1. s. 225-234.

Bibtex

@article{d0d70cba512a40c08706677ef40a5e59,
title = "TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients",
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.",
keywords = "Former LIFE faculty, TIMP-1, HER2, TOP2A, Prediction, Breast cancer, NCIC CTG MA.5",
author = "Hertel, {Pernille Br{\ae}mer} and Dongsheng Tu and Ejlertsen, {Bent Laursen} and Jensen, {Maj-Britt Raaby} and Eva Balslev and Shan Jiang and O'Malley, {Frances P.} and Pritchard, {Kathleen I.} and Shepherd, {Lois E.} and Annette Bartels and Nils Brunner and Nielsen, {Torsten O.}",
year = "2012",
doi = "10.1007/s10549-011-1896-1",
language = "English",
volume = "132",
pages = "225--234",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - TIMP-1 in combination with HER2 and TOP2A for prediction of benefit from adjuvant anthracyclines in high-risk breast cancer patients

AU - Hertel, Pernille Bræmer

AU - Tu, Dongsheng

AU - Ejlertsen, Bent Laursen

AU - Jensen, Maj-Britt Raaby

AU - Balslev, Eva

AU - Jiang, Shan

AU - O'Malley, Frances P.

AU - Pritchard, Kathleen I.

AU - Shepherd, Lois E.

AU - Bartels, Annette

AU - Brunner, Nils

AU - Nielsen, Torsten O.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Former LIFE faculty

KW - TIMP-1

KW - HER2

KW - TOP2A

KW - Prediction

KW - Breast cancer

KW - NCIC CTG MA.5

U2 - 10.1007/s10549-011-1896-1

DO - 10.1007/s10549-011-1896-1

M3 - Journal article

C2 - 22160637

VL - 132

SP - 225

EP - 234

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -

ID: 37445199