According to a new study conducted by researchers from the University of Manchester in the U.K., believe that a key biological apparatus may provide an explanation for the first time on why women with dense breast tissue have a higher risk of contracting breast cancer.
The University of Manchester research team has been collaborating with IBM Research in the US and Cyprus over the course of the study, which was funded by one of the UK's leading breast cancer charities and research organizations, Breakthrough Breast Cancer.
"We know that high breast density can greatly increase a woman's breast cancer risk as well as other factors such as aging, family history and presence of mutations in genes such as BRCA 1 and BRCA 2, " said Prof. Michael Lisanti, from the University of Manchester.
"What no one has fully appreciated before are the underpinning mechanisms at play. Using a bioinformatics approach, we have identified the relevant signaling pathways that make dense breast tissue more favorable for tumor formation,” Lisanti added.
Utilizing structural cells called fibroblasts from high-density breast tissue to produce a "molecular signature," the researchers discovered that a cell communication network called JNK1 demonstrated more activity in fibroblasts from high-density breast tissue than in lower-density breast tissue.
Cells are instructed by this network to release chemicals that cause inflammation, which can spur on the formation of tumors.
“Research expands on the early work by the London surgeon Stephen Paget, who proposed the 'seed and the soil' hypothesis, now over 125 years ago. In this paradigm, the 'seeds' are the cancer cells and the 'soil' is the tissue in which they grow,” said joint-senior author on the paper, Dr. Federica Sotgia.
"Our research has identified the right soil for seeds to flourish by looking at the micro-environment in the breast and examining the mechanisms at play. This can help us with designing new preventative trials, to develop and test new therapies, which might prevent progression on to cancer. Current cancer treatment often focuses on targeting cancer cells, but is not focused on targeting the fibrotic connective tissue, that may develop first, before you have cancer,” she added.
Therefore, the team believes that using drugs to mark this network and obstruct it from communicating with cells could offer a possible treatment for women with breast cancer. This theory is supported by the researchers' finding that the molecular signature of the fibroblasts from high-density breast tissue matches the signature of fibroblasts from breast tumors.
In the next phase of their work, the researchers will consolidate with other "world-leading" experts in cancer signaling, including Prof. Nic Jones, director of the Manchester Cancer Research Centre (MCRC) and Cancer Research UK chief scientist, who heads the Cell Regulation Laboratory, and breast density specialist Prof. Tony Howell.
"At least 50% of cancer risk is genetic, but activated cell stress signaling could potentially be reduced by dietary or lifestyle intervention. This research should help with a cancer prevention strategy, rather than waiting to treat the cancer once it arrives,” said Howell.
"This analysis of breast density provides a new framework for additional experimental exploration in breast cancer research. This has important clinical and translational implications for stratified medicine and breast cancer prevention,” noted Jones.
