New factors that can predict breast cancer recurrence defined
Discovery has the potential to also benefit treatment choices

Date:
April 22, 2022
Source:
Georgetown University Medical Center
Summary:
Genetics and other factors that can determine if a woman is at risk
for a recurrence of breast cancer have been identified, providing
new research avenues for preventing a new tumor from developing.



FULL STORY ========================================================================== 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 finding appeared April 22, 2022, in Scientific Reports.

The researchers focused on breast epithelial cells, which are the layer of cells that form the ducts and lobes which make 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.

The scientists 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.

Even though 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 percent of women, sometimes years after
surgery; people with hormone-receptor positive breast cancer have the
highest risk of recurrence.

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.

"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
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. 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.

This research effort was greatly aided by the conditionally reprogrammed
cells (CRC) technique that was invented and patented at Georgetown. This
study used CRC for the initial isolation of epithelial cells. 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. 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 CRC technique compared
to conventional methods.

"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."
In addition to Furth, the other authors from Georgetown include Sahar J.

Alothman, Keunsoo Kang, Xuefeng Liu, Ewa Krawczyk, Redha I. Azhar, Rong
Hu, David Goerlitz and Bhaskar V. Kallakury, Funding includes grants
from NCI (RO1CA112176 and P30CA051008) and the King Abdullah Scholarship Program, Kingdom of Saudi Arabia.


========================================================================== Story Source: Materials provided by
Georgetown_University_Medical_Center. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Sahar J. Alothman, Keunsoo Kang, Xuefeng Liu, Ewa Krawczyk, Redha I.

Azhar, Rong Hu, David Goerlitz, Bhaskar V. Kallakury, Priscilla
A. Furth.

Characterization of transcriptome diversity and in vitro behavior
of primary human high-risk breast cells. Scientific Reports, 2022;
12 (1) DOI: 10.1038/s41598-022-10246-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220422094313.htm

--- up 7 weeks, 4 days, 10 hours, 51 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)