Breast cancer cells.

Ahead of the first in a series of pub-based science talks, called “SciBar” this evening (16 August), Hayley Frend explains why fundamental knowledge about the mammary gland is still needed and how research in the field will impact on the treatment of breast cancer in the future.

It’s difficult to accept that it can take a long, long time before a breakthrough in basic biology reaches the stage where a clinical treatment can be produced.

Hayley Frend

Search for the words “breast cancer” and “breakthrough” on any online news service and you are likely to turn up hundreds of articles from the last 12 months alone. “Breakthrough breast cancer drug extends life of victims,” one article promised in June this year, for example. “Genetic testing could pave the way for breast cancer ‘silver bullets’,” claimed another.

Yet for all the stories auguring life-saving treatments, there are as many which betray the fact that breast cancer remains the most common form of cancer in the UK. “How much influence do we actually have on whether we develop breast cancer,” one sobering article asked in the wake of stories about scientific advances a few weeks ago. Another piece drew attention to the disturbing statistic that breast cancer recurs in almost one in four patients.

The truth is that in spite of the frequency with which we hear about promising research on the subject, and although survival rates are unquestionably increasing, breast cancer is still a major problem. In the United Kingdom, it affects 50,000 people every year. An estimated 32 women die of breast cancer every single day. And predictably, the less developed a nation is, the higher the death toll from breast cancer tends to be.

“People get very frustrated when the media mention a breast cancer breakthrough of one sort or another and then nothing seems to come out of it,” Hayley Frend, a second year PhD student at the University of Cambridge whose work focuses on mammary glands, says. “It’s difficult to accept that it can take a long, long time before a breakthrough in basic biology reaches the stage where a clinical treatment can be produced. Each so-called breakthrough is probably better described as just another piece in the puzzle.”

Frend works with Professor Christine Watson in the University’s Department of Pathology, under the Wellcome Trust’s four-year stem cell programme. The research group of which she is a part is involved in researching how the mammary gland develops. On Thursday this week (August 16), she will be taking part in Cambridge’s first British Science Association “SciBar” - a public science event, which, as the name suggests, usually happens at a venue serving alcohol. The talk is entitled “Breast Cancer - Back To Basics”.

SciBar speakers are invited to give a short and informative presentation about their area of research or expertise, or, as Frend puts it, to “justify their work and its relevance to a general audience.” The audience themselves are invited to ask questions and interrogate the issues at stake, which can be a daunting but healthy experience for the academic involved.

After decades of rapid advancement in our understanding of human biology, it seems surprising that something as fundamental as the mammary gland should still be the subject of so much scientific inquiry. In truth, though, the “back to basics” theme of Frend’s talk vouches for the fact that we still have much to learn about this fascinating organ. Understanding the basic biology of the breast is the only way to ascertain what is happening when it goes wrong, so it is also the only way to create effective treatments - or breakthroughs - in breast cancer.

A more complete understanding of the mammary gland has proven elusive until now because, while most organs in the human body are fully developed before birth, the mammary gland is a more dynamic environment which it is difficult to track. At birth, there is a very basic structure present in a large fat pad. When a girl enters puberty, the gland grows further as hormones are released. If the woman then becomes pregnant, it develops further, but, after weaning, the glandular structure dies back again. Of course, if the woman becomes pregnant again, this process is repeated.

The upshot is that unlike other organ systems, the mammary gland is not fixed in its development, and that makes it harder for a scientist to understand it. Researchers struggle, for example, to identify stem cells or aspects of its genetic functioning. This is why “breakthroughs” in understanding and treating the breast when something goes wrong are necessarily fundamental and sometimes seem trivial to a non-scientist.

One recent breakthrough, for example, involved scientists essentially getting to grips with a single gene and how it might be regulated in a particular cell type. A specific form of breast cancer may, or may not, ultimately be understood to emanate from that cell, so this knowledge could prove critical to treating the cancer and the gene itself may in time become a therapeutic target. Until we know more about how the breast develops, however, the ultimate value of this research remains difficult to quantify. Given the fact that lives are at stake, it is nevertheless essential.

What is becoming clear is that breast cancer has many variants and the number of subdivisions is growing. “It is rising all the time,” says Frend. “The more we learn about molecular markers of cancer, the more sub-types we are likely to find. In the long term, however, that will also enable more focused treatments.”

Two large subdivisions of breast cancer are basal and luminal - terms relevant to the cell types found within the tumour. Until recently, it was thought that this was also the cell type where the cancer began, but now it appears that basal breast cancer can start in luminal cells. How one can give rise to the other is a complex problem and, again, an example of why fundamental knowledge about the mammary gland is needed.

The work of Frend’s research group covers numerous aspects of the gland’s functioning. A recent project involved identifying the mammary gland stem cells which are thought to be responsible for the growth of the gland during pregnancy, while another focused on which cells die, and why, when the gland regresses after weaning. Yet the overall message remains the same - the more we understand about how this gland functions, the better we can explain what is happening when it goes wrong and breast cancer occurs. And the more we understand, the better placed we are to invent new drugs to treat cancer and save lives.

A living mammary gland is, of course, difficult to study. Frend herself has been involved in a project which responds to this by creating a model, synthetic mammary gland in a dish. First, a scaffold is created using collagen and hyaluronic acid in which fat cells are implanted. This creates a structure which looks like the fat pad, and to which mammary cells can be added to resemble a real-life gland. Once a working model is complete, different cells and chemicals can be added to imitate different reactions and processes within real mammary glands.

As part of her talk, Frend is threatening to do something similar live in the pub, “by modelling a breast using members of the audience.” Whether this will happen and what it will entail remains to be seen. Expect to learn something new about this important fundamental research, however, along with a few surprises on the way.

The inaugural SciBar event, “Breast Cancer - Back to Basics”, will take place in the Emperor Pub, 21, Hills Road, Cambridge, on Thursday, 16 August at 6pm. Free food will be provided. Further details are available on Facebook at: https://www.facebook.com/SciBarCambridge/events


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