Scientists from The University of Manchester working with IBM Research have identified a key biological mechanism that for the first time explains why women with dense breast tissue are at greater risk of developing breast cancer.
The research, published today in the journal Cell Cycle, has important implications for future cancer prevention and treatment.
Women with higher breast density-detected on mammograms-have more compacted breast tissue and are more likely to develop breast cancer, but until now the reasons for this have been unclear.
Manchester scientists, funded by leading UK research organization Breakthrough Breast Cancer, worked with IBM researchers and academics in the USA and Cyprus to uncover the biological mechanisms at play. Their findings could help to improve breast cancer prevention by targeting these specific biological mechanisms with cancer therapies in at-risk patients and could potentially lead the way for a new strategy for the use of preventative treatments.
Professor Michael Lisanti, from The University of Manchester, part of Manchester Cancer Research Centre, said, "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.
"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.
"This signaling pathway could be used as a biomarker to identify women at higher risk of breast cancer more accurately and earlier than the current methods. Furthermore, there are drugs out there that block these pathways, so that these women could be offered effective chemoprevention."
The researchers used structural cells, called fibroblasts, from high-density breast tissue to generate a molecular signature. This signature showed that a cellular communication network called JNK1 was activated to a greater extent in fibroblasts from high-density breast tissue. The JNK1 network is known to instruct cells to release chemicals that create an inflammatory environment, and inflammation is known to be a driver of tumor formation.
The study team explained that blocking the JNK1 network could feasibly reduce the risk of, and potentially prevent, breast cancer in women with high density breast tissue. Interestingly, the molecular signature of the fibroblasts isolated from high density tissue also matched the fibroblasts found in breast tumors, meaning drugs that interfere with the JNK1 network could also potentially act as a treatment for women who already have breast cancer.
Dr Federica Sotgia, from The University of Manchester's Institute of Cancer Sciences and joint-senior author on the paper, said, "This 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 cancers cells and the 'soil' is the tissue in which they grow.
"Our research has identified the right soil for seeds to flourish by looking at the microenvironment 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."