SAN ANTONIOIn women with primary breast cancer, the tumor invasion
factors 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
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.