Tumor-biological factors uPA and PAI-1 as stratification criteria of a multicenter adjuvant chemotherapy trial in node-negative breast cancer

In axillary node-negative primary breast cancer 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therap y is only needed for those 30% of node-negative patients who will relapse a fter primary therapy and eventually die of metastases. Traditional histomor phological and clinical factors do not provide sufficient information to al low accurate risk group assessment in order to identify none-negative patie nts who might benefit from adjuvant systemic therapy. In the last decade va rious groups have reported a strong and statistically independent prognosti c impact of the serine pretense uPA (urokinase-type plasminogen activator) and its inhibitor PAI-I (plasminogen activator inhibitor type I) in node-ne gative breast cancer patients. Based on these data, a prospective multicent er therapy trial in node-negative breast cancer patients was started in Ger many in June 1993, supported by the German Research Association (DFG). Axil lary, node-negative breast cancer patients with high levels of either or bo th proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only Recruitment was continued until the en d of 1998 by which time 684 patients had been enrolled. Since then, patient s have been followed up in order to assess the value of uPA and PAI-I deter mination as an adequate selection criterion for adjuvant chemotherapy in no de-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an i mpact on future policies in prognosis-oriented treatment strategies.