DNA-methylation of the homeodomain transcription factor PITX2 reliably predicts risk of distant disease recurrence in tamoxifen-treated, node-negative breast cancer patients – Technical and clinical validation in a multi-centre setting in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group

2007 ◽  
Vol 43 (11) ◽  
pp. 1679-1686 ◽  
Author(s):  
Sabine Maier ◽  
Inko Nimmrich ◽  
Thomas Koenig ◽  
Serenella Eppenberger-Castori ◽  
Inga Bohlmann ◽  
...  
2008 ◽  
Vol 26 (31) ◽  
pp. 5036-5042 ◽  
Author(s):  
Nadia Harbeck ◽  
Inko Nimmrich ◽  
Arndt Hartmann ◽  
Jeffrey S. Ross ◽  
Tanja Cufer ◽  
...  

Purpose We recently reported DNA methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene to be strongly correlated with increased risk of recurrence in node-negative, hormone receptor–positive, tamoxifen-treated breast cancer patients using fresh frozen specimens. Aims of the present study were to establish determination of PITX2 methylation for routine analysis in formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and to test PITX2 DNA methylation as a biomarker for outcome prediction in an independent patient cohort. Patients and Methods Real-time polymerase chain reaction (PCR) technology was validated for FFPE tissue by comparing methylation measurements in FFPE specimens with those in fresh frozen specimens from the same tumor. The impact of PITX2 methylation on time to distant metastasis was then evaluated in FFPE specimens from hormone receptor–positive, node-negative breast cancer patients (n = 399, adjuvant tamoxifen monotherapy). Results Reproducibility of the PCR assay in replicate measurements (rs ≥ 0.95; n = 150) and concordant measurements between fresh frozen and FFPE tissues (rs = 0.81; n = 89) were demonstrated. In a multivariate model, PITX2 methylation added significant information (hazard ratio = 2.35; 95% CI, 1.20 to 4.60) to established prognostic factors (tumor size, grade, and age). Conclusion PITX2 methylation can be reliably assessed by real-time PCR technology in FFPE tissue. Together with our earlier studies, we have accumulated substantial evidence that PITX2 methylation analysis holds promise as a practical assay for routine clinical use to predict outcome in node-negative, tamoxifen-treated breast cancer, which might allow, based on future validation studies, the identification of low-risk patients who may be treated by tamoxifen alone.


2001 ◽  
Vol 37 ◽  
pp. S121
Author(s):  
F. Valcamonico ◽  
G. Grigolato ◽  
F. Donato ◽  
V.D. Ferrari ◽  
E. Simoncini ◽  
...  

2018 ◽  
Vol 26 (3) ◽  
pp. 815-820 ◽  
Author(s):  
S. E. Tevis ◽  
R. Bassett ◽  
I. Bedrosian ◽  
C. H. Barcenas ◽  
D. M. Black ◽  
...  

The Breast ◽  
2016 ◽  
Vol 29 ◽  
pp. 102-108 ◽  
Author(s):  
An De Groef ◽  
Marijke Van Kampen ◽  
Elena Tieto ◽  
Petra Schönweger ◽  
Marie-Rose Christiaens ◽  
...  

2017 ◽  
Vol 123 ◽  
pp. S118
Author(s):  
H.J. Park ◽  
K. Shin ◽  
J. Kim ◽  
S. Ahn ◽  
S. Kim ◽  
...  

2010 ◽  
Vol 8 (3) ◽  
pp. 111-112 ◽  
Author(s):  
E. Gravier ◽  
G. Pierron ◽  
A. Vincent-Salomon ◽  
N. Gruel ◽  
V. Raynal ◽  
...  

2000 ◽  
Vol 15 (1) ◽  
pp. 73-78 ◽  
Author(s):  
A. Prechtl ◽  
N. Harbeck ◽  
C. Thomssen ◽  
C. Meisner ◽  
M. Braun ◽  
...  

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.


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