Effect of EDCs on breast density
Breast Cancer UK in collaboration with Animal Free Research UK are pleased to announce a joint award of £90,000 to Professor Valerie Speirs, at the University of Aberdeen, to fund a PhD studentship under her supervision. The studentship has been awarded to Ms Kerri Palmer and began on October 3, 2018.
The aims of the research are to try and identify whether different endocrine disrupting chemicals can affect breast density, which can determine breast cancer risk. Professor Speirs’ research also aims to replace two currently used animal models of breast cancer, by using fully humanised animal-free models.
Details of the research: Examining how endocrine disrupting agents may modulate activity of fibroblasts generated from breast tissue of high and low mammographic density
Breast density or mammographic density refers to how breasts appear on a mammogram. Breasts are made up of glandular tissue and fat tissue, held together by connective tissue (which contains cells known as fibroblasts). High breast density means there is a greater amount of connective and glandular tissue, compared to fat tissue. Women are 4-5 times more likely to get breast cancer if they have high breast density compared to those with low breast density (1). High breast density is the most significant breast cancer risk factor for women after ageing (2).
Breast density is partly inherited, but is also influenced by the environment, and changes over a women’s lifetime (3). It increases in response to hormones such as oestrogen, although how this occurs at the cellular level is not fully understood. Environmental factors also increase breast density. These include diet, alcohol (4) and synthetic hormones (3) such as hormone replacement therapy. In addition to hormones produced by the body and synthetic hormones that are prescribed, we are exposed to low concentrations of numerous endocrine disrupting chemicals (EDCs) at different times throughout our lives. Some of these mimic the actions of oestrogen. Currently, it is unknown if these contribute to changes in breast density. It is also unclear why high breast density increases breast cancer risk, however it is believed to be associated with the activity of fibroblasts, which are cells found in connective tissue of the breast (5). Fibroblasts respond to hormones, but details of this are not fully understood.
Kerri will investigate the effects of oestrogen mimics on fibroblasts generated from human breast tissue, using a novel 3D in vitro human mammary gland model. This model uses different breast cell types grown together and represents the human breast more closely than one type of breast cell grown in ordinary (2D) cell culture or using animal models. The research will examine the effects of four oestrogen mimics on human fibroblasts derived from breast tissue of different breast density, in order to understand how these influence breast density and in turn drive breast cancer development. The oestrogen mimics that will be used include the plastics component bisphenol A, plant-derived compounds genistein and resveratrol and the anti-miscarriage pill, diethylstilbestrol, which is no longer in use. RNA sequencing will be conducted on selected fibroblasts to identify which genes are affected by exposure to oestrogen mimics. Molecular biology techniques will be used to switch off or "silence" these genes. These fibroblasts will be incorporated into 3D breast cell models to establish if this influences the development of pre-invasive breast cancer.
The long term objectives of the study are to identify biochemical pathways which mediate breast density, which could be modified to reduce the risk of breast cancer, and ultimately, identify a strategy which will help prevent breast cancer.
For more details about breast density and Professor Speirs' research project please see here
1. Boyd et al. (2011). Mammographic density and breast cancer risk: current understanding and future prospects. Breast Cancer Research 13(6): 223. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326547/
2. Sherratt, M. J. et al (2016). Raised mammographic density: causative mechanisms and biological consequences. Breast Cancer Research 18: 45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855337/pdf/13058_2016_Article_701.pdf
3. Huo, C. W. et al. (2014). Mammographic density a review on the current understanding of its association with breast cancer. Breast Cancer Research and Treatment 144: 479–502. https://www.ncbi.nlm.nih.gov/pubmed/24615497
4. Voevodina, O. et al. (2013). Association of Mediterranean diet, dietary supplements and alcohol consumption with breast density among women in South Germany: a cross-sectional study. BMC Public Health 13: 203 https://www.ncbi.nlm.nih.gov/pubmed/23497280
5.Luo H. et al. (2015). Cancer-associated fibroblasts: a multifaceted driver of breast cancer progression. Cancer Letters 361(2):155-163. https://www.ncbi.nlm.nih.gov/pubmed/25700776
Page updated August 13, 2018