Written by Bethany Hoernfeldt, Science Writer
A cost-effective and efficient laboratory technique developed by researchers at Georgetown Lombardi Comprehensive Cancer Centre has proved instrumental in gauging the risk for breast cancer recurrence.
In a recent study, scientists successfully isolated difficult-to-extract, high-risk breast epithelial cells using conditionally reprogrammed cells (CRC) – a novel laboratory technique. Grown in in three mammary-specific media, the cells preserved behavioural and transcriptome diversity that reflects different breast cancer recurrence risk profiles. This addresses an unmet need in the world of cancer genomics.
Beneath the surface of breast cancer recurrence
According to Priscilla Furth, the corresponding author of the study, approximately one in eight women in the developed world receive a breast cancer diagnosis. Breast cancer is a group of complex diseases that result from an interplay between genetic, lifestyle, environmental, and physiological factors. Faulty differentiation of mammary stem cells spurred by the menstrual cycle and pregnancy can also contribute to this process, as hormonal cycling can trigger extra renewing cell cycles. This increases the likelihood of dysregulated stem cell function, which subsequently increases the risk of cancer.
Although surgical techniques are advanced, some tumour cells can remain after the tumour is removed. These cells are difficult to extract and can contribute to the development of secondary breast cancer. In fact, late recurrence occurs in up to 15 percent of women and is more common with hormone positive cancers. To complicate matters, normal-appearing cells in the same breast are at higher risk for carcinogenesis.
Addressing unmet needs in cancer genomics
Previously, transcriptional (RNA) profiles derived from mouse epithelium were instrumental in understanding the effect of hormonal cycling on mammary gland development in humans. Other existing data includes a cellular blueprint of human breast tissue, information surrounding age-associated changes in gene expression, and comparative transcriptional data from individuals at high and normal breast cancer risk. However, prior to this study, transcriptional profiles for breast cancer risk prediction were lacking.
The solution was a cost-effective and efficient laboratory technique called CRC. It is the only system that can replicate both normal and cancer cells both quickly and indefinitely. Up to one million cells can be grown in a week and, using matrix-free scaffold-based nano-culture plates, the samples and their transcriptional profiles can be analysed in a variety of media while subjected to different hormone treatments.
CRC addresses several key problems. Firstly, compared to previously used methods, the scientists succeeded in isolating difficult-to-extract high-risk breast cells using the novel technique. Secondly, it eliminates the need for a fibroblast feeder layer which minimises contamination by fibroblasts and other cells that grow quicker in media than epithelial cells. Lastly, CRC technology preserves progenitor cells and would allow at-risk cells to be renewed as new technologies and questions rise.
A first step in unravelling the mystery of breast cancer recurrence
After a patient underwent a mastectomy to remove cancerous breast tissue, non-cancerous epithelial tissue from the same breast was donated to the researchers. Using CRC, they isolated the cells and assessed diversity within transcriptional profiles using RNA-Seq. The transcriptome diversity revealed recognised indicators for breast cancer despite the healthy appearance of the cells. The data reflects various risk profiles which may drive further research on tumour prevention and the development of more precise diagnostic tools.
“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, corresponding author of the study. “We hope that our findings will help lead to more precise and directed screening in the future, sparing women unneeded procedures.”
Although these diagnostic platforms may prove challenging and time-consuming to build, CRC has rendered a previously daunting task feasible, so that we may continue to continue to unravel the mysteries surrounding cancer recurrence.
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