SAN ANTONIO, Texas—The 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.
Individualized Therapy
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.
