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Meaning Of Agonist And Antagonist”]

In patients with affected lymph nodes, the benefits of CT and HT and their relation to uPAPAI were again qualitatively and even quantitatively very close to those seen in the analysis of all patients and in the group with affected nodes. To allow tailored therapy concepts that take the individual tumor biology into account, factors are needed that guide physicians with regard to the estimation of patient prognosis and the prediction of therapy response.Thus far, uPA and PAI are the only novel tumor biological factors that have reached levelI evidence with regard to their prognostic impact in primary breast cancer. Yet, it is not known what kind of adjuvant therapy would be most beneficial for patients who had been grouped into different risk categories according to their uPA and PAI levels in the primary tumor tissue.This paper demonstrates that uPA and PAI have not only a clinically relevant prognostic but also predictive impact in primary breast cancer.Ideally, the gold standard for determining predictive information is a properly designed prospective study.However, for ethical reasons, new studies cannot include control groups of patients without adjuvant systemic therapy.On the other hand, large retrospective data sets containing substantial patient numbers with and without adjuvant systemic therapy are available for analysis.In general, it is quite difficult to ascertain predictive information from retrospective data in breast cancer, because adjuvant treatment decisions were made on the basis of guidelines in force at that time taking into account prognostic factors.Such factors thus act as confounding variables for retrospectively analyzing efficacy of adjuvant treatment.Moreover, different adjuvant treatment policies were used in different centers.Nonetheless, for factors that do not strongly correlate with treatment decisions, the problem of confounding can be reduced by various methods, in particular, by appropriate use of XY1 multivariate analysis and stratification.Because these requirements are satisfied rather well by uPA and PAI, the results presented in this paper should indeed reflect the predictive properties of uPA PAI.An important step in deconvoluting the confounding factors in retrospective data is to introduce a multivariate statistical scoring model using as much of the information as possible in the other variables.A good scoring model will reduce the unexplained variation in the data and improve the chances of seeing interactions if they are present.The only exception to the strategy of continuous variables were the factors uPA and PAI themselves, for which previously optimized cutoffs, validated in a prospective multicenter trial, were applied.The present paper confirms that uPAPAI have a significant impact on patient outcome but also provides additional evidence supporting their use in the clinic by demonstrating how effects of adjuvant systemic therapy differ in patients classified according to uPAPAI, primary breast cancer patients with low uPAPAI generally benefit from adjuvant endocrine and CT.However, the benefits of CT are strongly enhanced in patients with high uPAPAI.It is important to note that patients with high uPAPAI also benefit from adjuvant endocrine therapy, even though adjuvant CT has a greater beneficial impact on their DFS.Nodenegative patients with low uPAPAI have a very low risk of relapse per se.

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