Breast cancer research
Valerie Speirs, Professor of experimental pathology & oncology at the University of Aberdeen, is leading a three year study with PhD student Kerri Palmer, that hopes to identify an effective strategy for preventing breast cancer. The project, in collaboration with our friends at Breast Cancer UK, is exploring if hormone disrupting chemicals we find in our environment are making the breast more vulnerable to breast cancer.
How does our research help humans?
Breast cancer is the most common female cancer, affecting around 55,000 women in the UK every year. Women have a 1 in 8 chance of getting breast cancer in their lifetime, while men have a 1 in 870 lifetime chance.
When patients go through breast cancer screening, mammogram images are taken. These images reveal dark and light areas of the breast, which represent breast tissue density. Having dense breast tissue is a risk factor for breast cancer development; women with dense breasts have a four-to-six times increased risk of developing the disease.
We are also being exposed, increasingly, to a number of chemicals in our environment that can mimic the action of hormones. Researchers know that breast density is modified by hormones, but they don’t exactly know how it happens, or if hormone-mimics have the same effect.
Could fibroblasts be responsible for breast cancer development?
Fibroblasts are cells that contribute to breast tissue density. They are found all over the body, including in the breast. Their main job is to make the structural framework that holds together cells in a tissue. They can also influence other cells found in the breast – the same cells that breast cancer causes to uncontrollably grow and develop into tumours. Scientists believe that women with dense breasts have a higher risk of developing breast cancer due to the activity of fibroblasts.
Fibroblasts can respond to hormones. If we can understand how hormones affect fibroblasts and therefore how they influence breast density, then we may be able to uncover ways to target fibroblasts, to reduce the risk of people developing breast cancer and save more lives.
What is breast tissue density?
The density of breast tissue varies between different women. Some breasts contain mostly fat, which appears dark on a mammogram. These breasts are therefore termed ‘low mammographic density’. Other breasts contain mostly standard cells that make up the breast and other types of cells that help support and connect the breast cells together. These types of cells are more dense than fat cells and so appear lighter on a mammogram. Breasts like this are thus termed ‘high mammographic density’. Women with dense breast tissue (high mammographic density) have an increased risk of developing breast cancer.
What are endocrine disrupting chemicals and how do they affect breast tissue?
Chemicals that can mimic the action of hormones are known as endocrine disrupting agents. These agents can be naturally occurring (such as those found in some types of plants) but most are artificial (such as those found in some plastics, personal care products, cosmetics, domestic cleaning products, food and drink).
The hormone oestrogen can stimulate cell growth in both healthy and potentially cancerous cells. Breast tissue is sensitive to oestrogenic hormones. Continued low-level exposure to endocrine disrupting agents over time can interfere with (or mimic) the action of oestrogenic hormones. This can sometimes have detrimental effects in hormone-sensitive tissues, such as breast tissue, as it can trigger events in cells that result in unwanted responses.
How are we studying breast cancer development using human-relevant animal free research?
Through engagement with pathologists, who concentrate on what tissues look like in order to diagnose disease, the team are building animal free breast cancer models. These models reflect human disease because the researchers are ensuring that they look and behave like human breast tissues.
Human disease can only be examined properly using human tissue.
Importantly, the research is not use any animals or animal-derived materials. It is being carried out using fibroblasts generated from human breast tissue, of consenting patients, with different mammographic densities.
The team are working with clinicians to explore how human breast fibroblasts respond to endocrine disrupting agents. Complex 3D laboratory models are used to examine how this may contribute to breast cancer development.
Our models are helping us address how cells called fibroblasts may affect breast cancer development. This question cannot be modelled successfully in mice because human fibroblasts are very rapidly replaced by mouse fibroblasts when they are used in mouse models.
What is the impact on animals used for research?
Professor Valerie Speirs identified, during a search of the scientific literature in July 2017, 3016 publications in the last 5 years that have used animal models to study breast cancer, including 109 with UK-based authors. These were mainly mouse models and included the 3 major types of models: genetically engineered mouse models, patient-derived xenografts (transplants) and cell line-derived xenograft models.
A typical mouse experiment usually includes four groups of 10 mice. Of these publications from UK groups, it is estimated that more than 4000 mice would have been killed, excluding any required for breeding programme, which can often run into thousands. The severity levels for these types of experiments are mostly moderate.
Professor Speirs’ research aims to replace two animal models of breast cancer, which are used currently by scientists, by using fully humanised animal free models.