Conditionally Reprogrammed Cells Help Identify Factors for Breast Cancer Recurrence

Researchers in Washington, DC have identified genetic and other factors that can help determine if a woman is at risk for breast cancer recurrence. The findings may help reduce misdiagnosis and contribute to better therapeutic strategies.

Although surgical techniques continue to improve, undetectable microscopic pieces of tumor can remain and are one factor for recurrence of breast cancer in up to 15% of women, sometimes years after surgery. People with hormone-receptor positive breast cancer have the highest risk of recurrence.

“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,” says Priscilla Furth, M.D., professor of oncology and medicine at Georgetown Lombardi Comprehensive Cancer Center. “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 current work, published in Scientific Reports, focused on breast epithelial cells, which are the layer of cells that form the ducts and lobes that produce milk during lactation. The investigators extracted these cells from donated non-cancerous 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 transcriptome—the entire collection of RNA sequences in a cell. 

The work was greatly aided by the conditionally reprogrammed cells (CRC) technique that was invented and patented at Georgetown. CRC 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. This study used CRC for the initial isolation of epithelial cells. Previously, epithelial cell cultures were often contaminated with the other cell types, particularly fibroblasts that grow very quickly in culture compared to epithelial cells. Primary tumor cells also can be difficult to isolate, but the researchers had increased success using the CRC technique compared to conventional methods.

When analyzing the 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.

The researchers note 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. Stem cells are self-renewing and related to growth and development. Mammary stem cells are adult stem cells that can differentiate, or change function, into specialized mammary epithelial cells. If these 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.

“Many of our cancer survivors say to me, ‘please do work that will benefit my daughter.’ My response is that’s why I’m in the field of cancer prevention,” says Furth. “Anything we can do to prevent the occurrence or recurrence of cancer is a significant step forward and we think this finding may be an important contribution to reducing misdiagnosis as well as point to ways to develop better therapies to treat the disease.”