4 months ago
The causes of many breast cancers remain unknown. In the UK more is spent on breast cancer research than any other type of cancer. However, only a very small proportion of this research is devoted to causes, and even less to the role of environmental chemicals. This is despite strong scientific evidence exposure to chemicals that disrupt hormones (known as endocrine disrupting chemicals or EDCs) plays a significant role in breast cancer risk. Which chemicals cause the most harm and how? What levels are harmful? Over what time scale? Are there periods of increased susceptibility such as in the womb? How harmful are mixtures of chemicals? Our research programme aims to answer these questions.
King’s College London
Dr Michael Antoniou and Dr Robin Mesnage studied bisphenols. Bisphenols are found in hard plastics, linings of cans, and till receipts. They are now routinely detected in human body fluids and tissues. Bisphenol A (BPA) was once the most commonly used bisphenol; its use is now restricted in most products because it mimics the natural hormone oestrogen and so may increase breast cancer risk. The researchers showed that alternative bisphenols, replacing BPA, could also mimic oestrogen. Some were more oestrogenic than BPA. Their results were used to support the introduction of a new Bill by the State of New York to prevent children from being exposed to harmful bisphenols. Their findings were published in Toxicological Sciences and highlighted by both the Editor-in-chief and the US Environment Protection Agency. We are now funding a follow-on project which examines the oestrogenic effects on breast cells exposed to mixtures of bisphenols.
In an earlier project, the King’s College researchers examined the effects of the herbicide, glyphosate, on breast cancer cells. Their study showed glyphosate and its commercial formulation, Roundup, are oestrogenic, but only at very high levels. Long-term exposure to low concentrations of glyphosate has been shown to cause an increase in mammary cancer in rodents, but this is not because glyphosate is acting as an oestrogen mimic.
University of Reading
A study led by Professor Philippa Darbre was the first to demonstrate the presence of three different UV filters in human breast tissue. UV filters are used in sunscreens to protect us from skin cancer, and in certain personal care products, where they act to slow product deterioration. All UV filters examined are oestrogenic so may increase breast cancer risk. The results were published in the Journal of Applied Toxicology. The findings were also reported in the media (e.g. here).
University of Leeds
Dr Laura Matthews’ research studied changes in nuclear receptor activity in normal breast tissue compared to those in different types of breast cancer tissue. Nuclear receptors are proteins that control gene expression and are potential drivers of breast cancer development. Distinct nuclear receptor profiles were found to be associated with different types of breast cancer. These results help to assess which drugs and environmental chemicals are more likely to be associated with breast cancer, helping to identify potential risk factors as well as new strategies for breast cancer treatment. The research was highlighted by the Society for Endocrinology at their annual conference, resulting in extensive news coverage (e.g. ITV news).
Dr James Thorne is currently being funded to investigate the role of oxysterols in breast cancer. Oxysterols are chemicals resulting from the breakdown of cholesterol, a fat-like substance made by the body, and found in some foods. Some oxysterols may be associated with increased breast cancer risk, its recurrence and spread, and resistance to drug treatments. Initial funding led to the successful development of a novel technique that measures oxysterols in cell culture and breast tissue. Crucially, it only requires a very small amount of tissue; less than that from a typical biopsy. We awarded Dr Thorne a follow-up grant which is co-funding a PhD studentship, awarded to Alex Websdale. He is investigating the role of oxysterols in the progression of triple negative breast cancer, a less common but often aggressive type of breast cancer, which is more difficult to treat. He is looking to see whether different oxysterols are present in different tumour types and if their presence can predict breast cancer relapse. His work will also investigate whether a diet rich in fruit and vegetables can alter oxysterols produced by the body, thereby helping to prevent breast cancer recurrence.
University of Brunel
Breast Cancer UK supports novel research techniques that can replace experiments using animals. Dr Elisabete Silva is a pioneer in this field. Using an innovative three-dimensional breast cell model, she showed that low, environmentally relevant concentrations of oestrogenic EDCs (propylparaben, BPA, DDT and benzophenone-3) caused changes resembling early stage breast cancer. When mixtures of the chemicals were used, changes were more significant. The project we are now funding examines the effect of combinations of EDCs and saturated fats (that may arise from a high-fat diet) on the early stages of breast cancer. This uses an exciting new 3D breast cancer model system known as “Breast-on-chip”. This method allows a constant flow of nutrients and communication between different cells, reproducing more closely how breast cells behave in the body.
University of Aberdeen
Breast Cancer UK has teamed up with Animal Free Research UK to co-fund a PhD studentship supervised by Professor Valerie Speirs examining the effects of EDCs on breast density using a 3D breast cell model. Apart from ageing, high breast density is the biggest breast cancer risk factor for women. It increases in response to oestrogen, so may be affected by EDCs that mimic oestrogen. Our student is Kerri Palmer, who initially worked on the effects of BPA on breast cells. This work demonstrated errors in the measurement of BPA concentrations and was published as a letter in The Lancet Diabetes and Endocrinology.
Scientific evidence to help prevent breast cancer
We are proud to be supporting these projects and intend to expand our funding programme. Despite the Covid-19 pandemic, all our researchers are working hard, despite not always able to access their laboratories. They have been analysing data, writing articles and reviews. We thank them for all their hard work, excellent output and their general support.
All this research informs our literature, content and our breast cancer prevention awareness work. It helps us to understand the impact of environmental chemicals on breast cancer risk. It provides further evidence to persuade policy-makers that robust regulation of endocrine-disrupting chemicals is necessary, a step towards our goal of preventing breast cancer in current and future generations.
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