SAN ANTONIO, TexasThe genetic signature of breast tumors seems to be a
powerful predictor of aggressiveness and metastatic potential, outperforming
the individual clinical parameters that have traditionally been used, according
to several presentations at the San Antonio Breast Cancer Symposium.
"Molecular profiling will soon impact the treatment of breast cancer,"
predicted Stephen Friend, MD, PhD, vice president of basic research at Merck
Laboratories in West Point, Pennsylvania. Molecular profiling, or gene
expression profiling, involves sophisticated pattern recognition that reveals
the activities within a tumor cell. The analysis of a host of genes, as opposed
to one biological marker such as estrogen receptor status, yields a true
"richness of data" and can be used to predict clinical outcome. "It allows for
categories of disease that are not simply defined as black or white," Dr.
Friend pointed out.
Studies at Merck/Rosetta Laboratories were able to identify patients at risk
for distant metastases and to use this information to guide clinical
decision-making, specifically, to direct adjuvant therapy only to patients who
truly require it.
Gene expression profiling subtypes each breast cancer tumor by its genetic
defects, a process that in the future should make individualized therapy
possible. The format for gathering this information is cDNA microarray
technology, used to rapidly screen and immunohistochemically stain tissue for
the presence of multiple genetic markers.
In a study using microarray cell lines, Swedish investigators identified a
list of new and partly uncharacterized genes associated with excellent vs poor
prognosis, and others associated with chemotherapy resistance and sensitivity.
At the Karolinska Institute, Stockholm, 524 patients underwent surgery for
breast cancer from 1994 to 1996, and 186 of these patients provided material
for RNA expression profiling. Of these, 37 were profiled on a small gene chip
with 10,000 genes and 149 were analyzed on a larger chip involving 33,000 genes
(some patients were excluded). Altogether, the microarrays yielded information
on 12,625 genes. Distant disease-free survival was assessed relative to the
array profiles in 134 patients.