TOP2A protein by quantitative immunofluorescence as a predictor of response to epirubicin in the neoadjuvant treatment of breast cancer

被引:16
作者
Moretti, Erica [1 ]
Desmedt, Christine [2 ]
Biagioni, Chiara [1 ]
Regan, Meredith M. [3 ,4 ]
Oakman, Catherine [1 ]
Larsimont, Denis [5 ]
Galardi, Francesca [6 ]
Piccart-Gebhart, Martine [7 ]
Sotiriou, Christos [2 ]
Rimm, David L. [8 ]
Di Leo, Angelo [1 ]
机构
[1] Hosp Prato, Sandro Pitigliani Med Oncol Unit, Ist Toscano Tumori, I-59100 Prato, Italy
[2] Inst Jules Bordet, Breast Canc Translat Res Lab JC Heuson, B-1000 Brussels, Belgium
[3] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA
[4] Harvard Univ, Sch Med, Boston, MA 02215 USA
[5] Inst Jules Bordet, Dept Pathol, B-1000 Brussels, Belgium
[6] Hosp Prato, Translat Res Unit, Ist Toscano Tumori, I-59100 Prato, Italy
[7] Univ Libre Bruxelles, Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium
[8] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA
关键词
anthracyclines; biomarker; breast cancer; quantitative immunofluorescence; TOP2A; TOPOISOMERASE-II-ALPHA; ADJUVANT CHEMOTHERAPY; ETOPOSIDE RESISTANCE; GENE AMPLIFICATION; TISSUE MICROARRAYS; COOPERATIVE GROUP; MYELOMA CELLS; EXPRESSION; HER2; ANTHRACYCLINES;
D O I
10.2217/fon.13.103
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aim: Anthracyclines are commonly used in breast cancer, although they lack validated predictive biomarkers. We explored the interaction between TOP2A protein by quantitative immunofluorescence (QIF) and anthracycline sensitivity. Patients & methods: Patients with estrogen receptor-negative breast cancer received neoadjuvant epirubicin. Pretreatment biopsies were analyzed using AQUA((R)). Total, cytoplasmic (C) and nuclear (N) TOP2A protein concentrations were expressed as QIF scores and compared with pathologic complete response (pCR), TOP2A by immunohistochemistry, TOP2A mRNA, TOP2A and HER2 gene status, and Ki-67 level. Results: In total, 76 cases were assessable. C, N, and total scores did not correlate with pCR, or other markers. The N:C ratio differed significantly by HER2 status. No pCRs occurred in patients in the lowest N:C quartile. Conclusion: Although no relevant correlation between TOP2A QIF scores and pCR was found, N:C ratio may have a negative predictive role, and may merit further exploration in a multifactorial predictive model that includes tumor and host factors.
引用
收藏
页码:1477 / 1487
页数:11
相关论文
共 43 条
[41]   Topoisomerase IIα 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].
Tanner, Minna ;
Isola, Jorma ;
Wiklund, Tom ;
Erikstein, Bjorn ;
Kellokumpu-Lehtinen, Pirkko ;
Malmstrom, Per ;
Wilking, Nils ;
Nilsson, Jonas ;
Bergh, Jonas .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (16) :2428-2436
[42]   Human Multiple Myeloma Cells Are Sensitized to Topoisomerase II Inhibitors by CRM1 Inhibition [J].
Turner, Joel G. ;
Marchion, Douglas C. ;
Dawson, Jana L. ;
Emmons, Nhchael F. ;
Hazlehurst, Lori A. ;
Washausen, Peter ;
Sullivan, Daniel M. .
CANCER RESEARCH, 2009, 69 (17) :6899-6905
[43]   Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy [J].
Vincent-Salomon, A ;
Rousseau, A ;
Jouve, M ;
Beuzeboc, P ;
Sigal-Zafrani, B ;
Fréneaux, P ;
Rosty, C ;
Nos, C ;
Campana, F ;
Klijanienko, J ;
Al Ghuzlan, A ;
Sastre-Garau, X .
EUROPEAN JOURNAL OF CANCER, 2004, 40 (10) :1502-1508