Researchers Target How Breast Cancer Forms

Investigators seek to stop women's cancers before it starts to form.

Researchers have uncovered new evidence in breast cancer that DNA changes are already present in healthy tissue.

Prior research showed there are key risk factors involved with an increased risk of cancer, such as family history, periods that start early, or menopause starting late.

At the time of exposure to these risks, these factors alter the genetic program slightly in breast cells, which are then memorized by the cells over time.

The system is called the epigenome, which is responsible for giving cells their identity and are vital to health and development. This carries a series of processes that control accessibility of human DNA sequence, which affects the interpretation of the genome and the affected cells.

The study was performed by researchers of the Department of Women’s Cancer at University College of London (UCL) and funded by The Eve Appeal and the European Union’s Seventh Framework Program. The findings, published in Nature Communications, were fueled by the need to determine how breast cancer is able to develop.

"Stopping women's cancers before they start is the ambition of our research program,” said Chief Executive of The Eve Appeal, Athena Lamnisos. “In order to do this we need to track cancer development right back to its earliest development and understand how it starts. This research is an important step towards understanding how molecular changes in healthy tissue can be detected. Once we can identify these changes we can then move on to developing ways to revert them."

The analysis used 668 breast tissue samples that ranged from women without cancer, normal breast and cancer tissue from women with cancer, and non-invasive and invasive breast cancer.

The results of the study showed that the normal tissue that was adjacent to the cancer was characterized by tens to thousands of epigenetic alterations. A large part of the detected epigenetic signature was enriched in the cancerous breast tissue.

This finding supported researchers’ belief that variable epigenetic signature marks susceptible precursor cells that are involved in the formation of the cancer.

These cases also had an association with worse prognoses and a decreased rate of survival.

"The application of these altered epigenetic signatures hold the key developing new interventions that could 'switch off' this epigenetic defect and hold the key to preventing cancer development,” said UCL Head of Department of Women's Cancer Martin Widschwendter.

"These new data show how epigenetic alterations, if detected early enough, could be used to identify women at higher risk of developing breast cancer,” adds lead computational biologist Andrew Teschendorff. “Since epigenetic alterations are reversible, it offers the potential to design preventive strategies. Our work further highlights the importance of inter-disciplinary work, combining clinical, biological and statistical expertise to make these findings possible."