This trial is active, not recruiting.

Condition breast cancer
Sponsor Martin-Luther-Universität Halle-Wittenberg
Start date September 2009
End date May 2011
Trial size 1000 participants
Trial identifier NCT01592825, GYN_Halle_01


The improvement of the healing rates for breast cancer is based to an important part on the consistent use of so-called adjuvant ("supporting ") medicamentous therapies, including chemotherapy. However this success has a price due to still inaccurate knowledge of the individual risk of relapse: a high number of unnecessary therapies are applied (over-therapy!). The invasion factors uPA (plasminogen activator of the urokinase type) and PAI-1 (uPA inhibitor) were described extensively as strong and independent prognosis factors with high clinical relevance for patients with node negative breast cancer. Compared to clinical and pathological factors (further: "traditional factors ") they show better estimation of the relapse risk leading to an avoidance of redundant adjuvant chemotherapy and may thus essentially contribute to the improvement of the quality of life in these women. In this study we aim to evaluate, how large the portion of the patients with early, operable, node negative breast cancer will be, in whom, by improved low-risk identification through uPA/PAI-1, adjuvant chemotherapy can be omitted.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective

Primary Outcomes

Event free survival
time frame: 2.5 years minimum observation time

Secondary Outcomes

Overall survival
time frame: 2.5 years

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - newly diagnosed breast cancer - no metastasis detected - operation for breast cancer - female patient - unilateral breast cancer - informed consent given - age min. 18 yrs. Exclusion Criteria: - metastasis of breast cancer - bilateral breast cancer - other cancer within the last 5yrs

Additional Information

Official title PiA Trial: a Cross-sectional, Multicenter, Consecutive Cohort Evaluating the Distribution of uPA/PAI-1 Versus St. Gallen Algorithm in >1000 Prospectively Included Patients
Principal investigator Eva J Kantelhardt, MD
Description The determination of the prognostic factors uPA/PAI-1 (further: "biological") is established and recommend by recent guidelines. However, so far data can only show their independent and strong prognostic influence. The absolute proportion of patients, which profit from the improved risk assessment, is only estimated from old trials with different patient populations. Depending upon assessment, the proportion of low risk patients by traditional risk assessment is 20 - 40%, by biological assessment 35 - 55% of all node negative patients. The data from investigations of historic populations are not reproducible now because of smaller tumor size at presentation due to diagnostic procedures (Screening, good public promotion). The effectiveness and clinical relevance of the risk assessment were already confirmed for the biological prognostic factors uPA/PAI-1 in node negative breast cancer in several retrospective and prospective trials as well as in a meta-analysis. Still these biological factors (or others!) are not yet established into nationwide clinical routine in Germany. This is due to higher expenditure of this method for the primary therapy (uPA/PAI-1 is determined in the shock-frozen tissue), on the other hand due to the absence of reimbursement. Therefore presently in many centres risk estimation and associated therapy decision is done by traditional assessment. In order to justify the higher expenditure and the additional costs by the uPA/PAI-1-determination, not only the clear proof of the advantage for the individual patient, but also the estimation of the extent of this advantage in all applicable patients is necessary. A first goal of this project is to compare the respective proportion of patients allocated as high- or low-risk by means of biological and also traditional prognosis factors in a defined consecutive patient cohort. The determination of uPA/PAI-1 should be established as standard procedure in the future. So far, the question discussed above referred mainly to patients with node negative breast cancer. In this group, the largest effect in saving chemotherapy is to be expected. Due to previous results we assume that also in node positive patients adjuvant chemotherapy may be saved in sub-group because of very small risk of recurrence. Therefore the determination of uPA/PAI-1 for this group of patients will also be done at the end of this study. A second goal of this project is it to collect data for risk assessment in node positive patients to be able to offer assistance in the future to perhaps give a better estimation of the individual risk of recurrence. Practically fresh frozen tissue will be taken, shock-frozen and stored from all consecutive patients operated in the five participating hospitals. The determination of uPA/PAI-1 will be performed in the research laboratory of department of Gynaecology at the University Hospital in Halle (Saale). A third goal is it to provide biological risk assessment by giving results of uPA/PAI-1 testing promptly to participating node negative patients. This information will be crucial in their decision for or against chemotherapy. Amendment 2 from June 12, 2012 (Steering committee E Kantelhardt, M Vetter, Ch Thomssen) A) Established prognostic factors (RNA level) will be evaluated in the context of uPA/PAI-1 and immunohistochemistry markers on samples from the frozen and FFPE tissue. The list of genes is submitted to the Ethics sommittee. B) Eplorative analysis of these factors concerning response to therapy will be done. C) Follow-up information will be collected after a minimum observation time of 2.5 years for all patients (in October 2013).
Trial information was received from ClinicalTrials.gov and was last updated in June 2012.
Information provided to ClinicalTrials.gov by Martin-Luther-Universität Halle-Wittenberg.