A team of researchers from Massachusetts General Hospital (MGH) and the biotechnology company Arcturus has discovered molecular changes occurring in early stages of breast cancer that characterize the aggressive potential of the tumor. Thus, early molecular analysis of biopsy samples may provide key information for choosing the best therapeutic options.

The researchers have identified a gene expression signature - groups of genes that are "turned on" in a tumor cell - that may represent the molecular basis for the current classification employed in the clinical management of breast cancer. The report was published in the Proceedings of the National Academy of Sciences.

"Our results are significant because they could change the way we think about the course of cancer progression. The molecular results provide new insight into the pathological changes that we have been observing for decades," says Dennis Sgroi, MD, of the Department of Pathology at MGH, co-senior author of the current report.

"Correlating new methods for diagnosing cancer based on gene expression signatures with currently accepted and proven pathological classifications is an important step in developing more effective strategies for diagnosing and treating breast cancer," he adds.

The authors note that it is widely held that breast cancer begins at a premalignant stage called atypical ductal hyperplasia, progresses into the preinvasive stage of ductal carcinoma in situ and culminates in the potentially lethal stage of invasive ductal carcinoma. Contrary to the researchers' initial expectations, the different stages of breast cancer showed remarkably similar molecular signatures or patterns of gene expression. Specifically, the preinvasive stages of breast cancer within one patient demonstrated a gene expression pattern that was highly similar to the pattern seen in the invasive, potentially lethal stage. This suggests that the genes conferring invasive behavior may already be expressed in the pre-invasive stage.

Intriguingly, distinct signatures were found in malignant cells extracted from tumors of different cancer grades - grade being another measurement by which tumors are classified. In other words, while tumors at all three of the traditional pathological stages do not significantly differ in their molecular signatures, there is a strong correlation between different gene expression profiles and differences in tumor grades. Additionally, these researchers have uncovered a subset of genes associated with high tumor grade and with the transition from the non-lethal stage to the potentially lethal stage.

The research teams are continuing their collaboration and are identifying unique molecular signatures correlating with other important properties of tumors, such as the probability of disease recurrence after treatment and tumor response to specific drug therapies.

SOURCES:
Proceedings of the National Academy of Sciences, May 14, 2003
Massachusetts General Hospital (http://www.massgeneral.org)