Genetics and other factors that can determine if a woman is at risk for a recurrence of breast cancer have been identified by investigators at Georgetown Lombardi Comprehensive Cancer Center, providing new research avenues for preventing a new tumor from developing. The discovery was made possible by an advanced technology developed at Georgetown Lombardi that allows laboratory researchers to greatly expand, or multiply, hard-to-extract breast tissue cells. The findings were published by Alothman et al in Scientific Reports.
The investigators focused on breast epithelial cells, which they extracted from donated noncancerous tissue in the same breast as the one that had cancerous tissue removed during a mastectomy. They were looking for numerous factors that could kick-start recurrence, but their main target was the entire collection of RNA sequences in a cell—the transcriptome—that helps determine when and where each gene is turned on or off in a cell.
When analyzing expanded epithelial cells from women who had chemotherapy before their surgery, the researchers found significantly altered RNA. In particular, they saw significant changes in genes that had previously been recognized as prognostic indicators for cancer.
Toward More Precise Screening
"When a person is diagnosed with breast cancer, we have several tools, including testing for genes such as BRCA1/2, to decide whether they should get certain kinds of chemotherapy or just receive hormonal therapy. But the tools we have are not as precise as we would like," said Priscilla Furth, MD, Professor of Oncology and Medicine at Georgetown Lombardi and corresponding author of the study. "About one in eight women are diagnosed with breast cancer in the developed world. We hope that our findings will help lead to more precise and directed screening in the future, sparing women unneeded procedures as we currently screen almost all women between the ages of 40 to 70, sometimes very aggressively."
The researchers also noted that there are implications for women who have not had breast cancer, as some of the RNA alterations were linked to mammary stem cell formation. If mammary stem cells get dysregulated, there is an increased potential for cancer. Cells from pregnant women were of particular interest to the researchers as pregnancy usually triggers extra renewing cycles in a cell, potentially increasing the risk of cancer.
Conditionally Reprogrammed Cells
This research effort was greatly aided by the conditionally reprogrammed cells technique that was invented and patented at Georgetown. This study used conditionally reprogrammed cells for the initial isolation of epithelial cells. This technique is the only known system that can indefinitely grow healthy as well as cancer cells; up to a million new cells can be grown in a week.
Heretofore, one of the key problems in studying these cells was that epithelial cell cultures were often contaminated with the other cell types, particularly fibroblasts, which grow very quickly in culture while epithelial cells grow a bit slower. Primary tumor cells also can be difficult to isolate but the researchers had increased success using the conditionally reprogrammed cells technique compared to conventional methods.
Disclosure: The study was supported by grants from the National Cancer Institute and the King Abdullah Scholarship Program, Kingdom of Saudi Arabia. For full disclosures of the study authors, visit nature.com.
