New factors that can predict breast cancer recurrence identified by investigators

Discovering genetics and other factors that can determine whether a woman is at risk for breast cancer recurrence has the potential to benefit from treatment options.

The discovery also has the potential to benefit treatment options

Researchers at Georgetown Lombardy Comprehensive Cancer Center have uncovered genetic and other factors that can predict whether a woman is at risk for breast cancer recurrence, opening up new research possibilities to prevent the development of a new tumor. This breakthrough is made possible by a cutting-edge technology created in Georgetown Lombardy that allows laboratory researchers to expand or multiply cells of difficult-to-extract breast tissue.

The result will be published today (22 April 2022) in the magazine Scientific reports.

The researchers focused on the breast epithelial cells, the layer of cells that make up the ducts and lobes that make milk during lactation. The investigators extracted these cells from non-cancerous tissue donated in the same breast as the one in which the cancerous tissue was removed during a mastectomy. Scientists have been looking for many factors that can lead to recurrence, but their main goal was a complete set of RNA The sequences in the cell – transcripts – that help determine when and where each gene in the cell is turned on or off.

Although surgical techniques continue to improve, microscopic pieces of the tumor can remain undetectable and are a factor in breast cancer recurrence in up to 15 percent of women, sometimes years after surgery; People with hormone receptor positive breast cancer are more likely to have a recurrence.

When analyzing the expanded epithelial cells from women who had undergone chemotherapy before surgery, the researchers found a significant change in the RNA. In particular, they saw significant changes in genes previously recognized as prognostic indicators of cancer.

When someone is diagnosed with breast cancer, we have many tools, including genetic testing such as BRCA1/2, to decide whether they should have certain types of chemotherapy or only receive hormone therapy. “But the tools we have are not as accurate as we’d like,” says Priscilla Forth, MD, professor of oncology and medicine at Georgetown Lombardy and corresponding author of the study. “One in eight women in the developed world is diagnosed with breast cancer. We hope our findings will help in more accurate and targeted screening in the future, sparing women unnecessary procedures because we currently screen almost all women between the ages of 40 to 70, Sometimes very forcefully.

The researchers also noted that there were effects in women who did not have breast cancer because some of the RNA modifications were linked to the formation of breast stem cells. Stem cells are self-renewing and are associated with growth and development. Breast stem cells are adult stem cells that can differentiate or change function into specialized mammary epithelial cells. If these cells are disorganized, there is an increased possibility of developing cancer. The cells taken from pregnant women were of particular interest to the researchers because pregnancy usually triggers additional cell renewal cycles, which can increase the risk of cancer.

This research effort has been greatly supported by the conditionally reprogrammed cell (CRC) technology invented and patented at Georgetown University. This study used CRC for the initial isolation of epithelial cells. CRC is the only known system in which healthy cancer cells as well as cancer cells can grow indefinitely. Up to one million new cells can be grown within a week. So far, one of the major problems in studying these cells has been that epithelial cell cultures have often been contaminated with other cell types, especially fibroblasts that grow very quickly in culture while epithelial cells grow slightly more slowly. It can also be difficult to isolate primary cancer cells, but researchers have had increased success using CRC technology compared to traditional methods.

“Many cancer survivors tell me, ‘Please do something that will benefit my daughter.’ My response is why I’m in the cancer prevention field,” says Forth. “Anything we can do to prevent the occurrence or recurrence of cancer is an important step forward and we believe this finding could be an important contribution to reducing misdiagnosis as well as pointing to ways to develop better treatments to treat the disease.”

Reference: “Characterization of transcriptome diversity and in vitro behavior of high-risk primary human breast cells” by Sahar J. Walthman, Kyunsu Kang, Zofeng Liu, Ewa Krause, Reza Ai Azhar, Rong Ho, David Gurlits, and Paskar F. and Priscilla A. Forth, April 22, 2022, Available here. Scientific Reports.
DOI: 10.1038 / s41598-022-10246-4

In addition to Forth, other authors from Georgetown include Sahar J. Walthman, Konso Kang, Xuefeng Liu, Ewa Krawczyk, Redha I. Azhar, Rong Hu, David Goerlitz, and Bhaskar V. Kallakury.

Georgetown University has patents issued and patent applications pending regarding the CRC technology described in this story. Leo is an inventor in the field of intellectual property. In addition, Georgetown University has licensed the patent rights to a marketing startup. Liu serves as a consultant to this company, and Georgetown has an ownership stake in the company.

Funding includes grants from the NCI (RO1CA112176 and P30CA051008) and the King Abdullah Scholarship Program, Saudi Arabia.

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