SAN ANTONIOIn women with primary breast cancer, the tumor invasion factors urokinase(Drug information on urokinase)-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) can predict benefit from adjuvant chemotherapy and should support clinical decision making, according to European investigators who for years have been studying the role of these two molecules in breast cancer. Nadia Harbeck, MD, of Technical University, Munich, Germany, described their most recent findings at the 25th Annual San Antonio Breast Cancer Symposium (abstract 7).
The two factors play a key role in tumor invasion, performing actions that are critical for the metastatic phenotype. They were the first novel biological factors to demonstrate solid clinical relevance in breast cancer by affecting prognosis. This was shown in a prospective randomized trial by the European Organization for Research and Treatment of Cancer (EORTC) and in a pooled analysis of more than 8,000 EORTC patients.
"The evidence and the availability of quality-controlled assays prompted us to include these factors among those we use to make clinical decisions in node-negative patients," Dr. Harbeck said. "We saw that these factors clearly differentiate the prognosis in patients who did not receive adjuvant therapy, either node-negative or node-positive patients." In patients who did receive adjuvant therapy in earlier analyses, she said, the differences between patients with low vs high levels of uPA and PAI-1 were diminished, and there was little prognostic impact.
In a prospective multicenter trial of node-negative patients, those considered at high risk by uPA and PAI-1 levels were randomized to observation (after loco-regional treatment) or chemotherapy. Results showed that chemotherapy reduced the risk of relapse in these patients. The high-risk patients who received no adjuvant chemotherapy had a significantly worse prognosis than the low-risk patients. Their risk was comparable to that of patients with three to four positive lymph nodes (Harbeck N et al: San Antonio Breast Cancer Symposium 2001, abstract 19).
"These were hints, but they did not prove that these factors were actually predictive, only that high-risk patients benefit from chemotherapy," she said.
The Current Study
The current study, therefore, was designed to determine whether relapses that would occur (predicted with conventional decision-making factors) could be avoided or delayed by measuring these invasion factors and administering chemotherapy to the high-risk group.