Investigating effects of per- and poly-fluoroalkyl (PFAS) substances on breast cancer development. 

Breast Cancer UK is pleased to announce we have awarded a grant of £99,272.48 to Dr Mark Wade and colleague Prof Jeanette Rotchell, University of Hull, to fund a Ph.D. studentship that will investigate whether PFASs play a role in breast cancer development and determine whether microplastics that can leach PFASs are found in breast tissue.

Project details

As well as genetic predisposition and lifestyle factors, exposure to environmental contaminants increase breast cancer risk. However, in many cases, how these contaminants influence breast cancer development is less well understood. Microplastics are small plastic materials that have entered the environment via industrial practices or have been degraded from plastics used in consumer products.

We know microplastics are present in our gut, blood, and can be breathed into the lungs. Microplastics are a potential source of harmful chemicals in our body, as they can stick to microplastics and then leach off them into the surrounding environment. A group of synthetic environmental toxins, called per- and poly-fluoroalkyl substances (PFASs), are known to stick to, and leach from, microplastics. However, the role of PFASs in health and disease is poorly understood. PFASs are of particular concern as they are used in consumer goods, are found in the environment and have been detected in humans.

This project will:

• investigate whether PFASs play a role in breast cancer development – normal breast cells will be exposed to PFASs at levels found in the blood and then assessed for characteristics often found in cancerous cells. The effect of long and short-term exposure will be analysed to see what changes occur immediately and which develop over time.
• determine whether microplastics that can leach PFASs are found in breast tissue – world-leading microscopy techniques will be used to analyse breast tissue donated by patients to see whether microplastics are present in the breast. This study will provide insight into the extent of microplastic contamination within the human body and will greatly enhance our understanding of whether PFASs can cause breast cancer.

Measurement of endocrine-disrupting chemicals (EDCs) in breast cancer

Breast Cancer UK is pleased to announce that we have awarded a grant of £100,000 to Dr Michael Antoniou and colleagues Cheryl Gillett and Francesca Mazzacuva, King’s College London, to assess the potential risks arising from endocrine-disrupting chemicals (EDCs) found in everyday products that can potentially lead to or promote breast cancer.

Project details

The growth of most breast cancers is dependent on the presence of the hormone oestrogen. As a result, exposure to chemical pollutants that mimic the action of oestrogen has been found to stimulate breast cancer growth. The aim of this project is to evaluate the presence of a broad range of oestrogen-like chemical pollutants in breast cancers. Chemical pollutants with oestrogen-like activity include:

• bisphenol and phthalate plasticisers used in food and drink packaging
• chemicals used in lotions to protect against sunburn
• parabens used as preservatives in foods, toiletries and cosmetics
• poly/perfluoroalkyl substances (PFAS) used in non-stick coatings, polishes, fire-retardant foams and stain-repellent finishes for fabrics
• some insecticides used in agricultural food production.

People are exposed to oestrogen-like chemical pollutants from multiple sources on a daily basis. Oestrogen-like chemical pollutants can build up in the fatty tissue part of the breast where they can fuel breast cancer growth.

The aim of this project is to screen frozen breast cancer samples for a broad range of oestrogen-like chemical pollutants. Both the cancer and non-cancerous fatty tissue from the same breast will be analysed. The results will be checked against the medical records of the person with breast cancer from which the tissue was obtained to assess if there is a connection between the amount and type of oestrogen-like chemical pollutants detected and breast cancer growth and spread.

This study will identify potential risks arising from oestrogen-like chemical pollutants that can potentially lead to or promote the growth of breast cancer.

Evaluating the effects of bisphenol A on breast cancer development 

Breast Cancer UK has awarded a grant of £99,272 to Professor Valerie Speirs and colleagues Professor Paul Fowler, Dr Felix Grassman, Ms Beatrix Elsberger and Mr Yazan Masannat, University of Aberdeen, to fund a PhD studentship which examines the effects of bisphenol A (BPA) on breast cancer development. The project is expected to begin in October 2022.

Background 

Hormones, especially oestrogen, can influence the development of breast cancer. Exposure to naturally occurring hormones is unavoidable. However, we can take steps to reduce exposure to synthetic chemicals which mimic oestrogen. One of these is bisphenol A (BPA), a chemical used to make many plastics and resins for nearly 60 years. BPA is present in lots of everyday products, foods and drinks at low concentrations. Scientists worry about BPA because it is linked with increased disease risks. BPA can interfere with hormone-sensitive organs, like the breast. While a single exposure to BPA is unlikely to result in the development of breast cancer, repeated and frequent exposure to low concentrations of this chemical could contribute to the development of breast cancer.  

Project details 

This project will build on information obtained during our current BCUK-funded work. We will discover if there are links between exposure to BPA and breast cancer development in women, using a range of approaches made possible by the team of experts we have assembled to tackle this problem. We will start with a thorough review of the scientific literature to identify possible ways that BPA acts on breast tissue. At the same time, we will “mine” the data in large cancer-related gene databanks. We will combine the information we harvest to design laboratory experiments that will confirm if BPA-sensitive genes contribute to breast cancer development. This will then help us discover if levels of these BPA-sensitive genes in a woman’s breast will affect whether she will suffer from more dangerous, aggressive, breast cancer. To join these findings together we will measure BPA in tissue samples donated by breast cancer patients. This will confirm if there is a relationship between BPA levels and breast cancer. This project will provide conclusive evidence surrounding the role of BPA in breast cancer. 

Biomonitoring and molecular toxicity profiling of bisphenol mixtures   

Breast Cancer UK is pleased to announce we have awarded a grant of £100,000 to Dr Michael Antoniou and colleagues Dr Robin Mesnage and Dr Ana Rodriguez-Mateos, King’s College London, to fund a PhD studentship which will undertake biomonitoring of UK residents to identify levels of bisphenols and evaluate the potential breast cancer initiating and growth promoting activity of bisphenol mixtures. The project is expected to begin March 2022.

Project details 

Chemical exposure that interferes within the body’s hormone systems has been linked to breast cancer. Large numbers of pollutants can have oestrogen hormone-like activities and can stimulate breast cancer cell growth. The aim of this proposal is to evaluate the breast cancer promoting activity of mixtures of oestrogenic pollutants known as bisphenols.   

Bisphenols are used in the manufacture of plastic bottles, resins and the plastic lining of cans, from which they leach into food and drink. Bisphenol A (BPA) is the prototypical member of this class of plastics components, which is now known to mimic the effects of oestrogen. Due to public concerns, industry has been replacing BPA with other bisphenol compounds to produce so called “BPA-free” products. However, our Breast Cancer UK sponsored work has revealed that bisphenols used as BPA replacements also possess oestrogen hormone-like activity with some being more potent than BPA, and which fuel breast cancer cell growth. However, the exact mechanisms by which bisphenol mixtures may stimulate the development and progression of breast cancer remain unknown. In addition, bisphenol mixtures to which the UK population is exposed daily is unknown.    

This project will further investigate the connection between bisphenol mixture exposure and breast cancer by undertaking two lines of research. First, we will analyse the urine of UK residents to identify which bisphenols people ingest. Second, we will evaluate the breast cancer-causing and promoting potential of realistic cocktails of bisphenols by assessing their ability to stimulate the growth of normal human mammary epithelial cells and alter these cells’ characteristics to a cancerous state.   

This study will identify potential risks arising from bisphenol ingestion that can potentially lead to, or promote growth of, breast cancer.  

Multifactorial impacts on early breast carcinogenesis – assessing the combined effects of preventable factors on breast cancer using a novel Organ-On-a-Chip platform.

Breast Cancer UK has awarded a grant of £43,360 to Dr Elisabete Silva and colleagues, Drs Ruth MacKay, Sibylle Ermler and Emmanouil Karteris, Brunel University London, to fund research that examines the role of EDCs and saturated fatty acids on early stages of breast cancer. The project began in February 2020 and will finish February 2022.

Background and details of the research 

Lifestyle factors and environmental contaminants, including endocrine disrupting chemicals (EDCs), play a role in breast cancer development but human studies linking EDCs to cancer are often inconclusive. This is mainly because EDCs are studied individually and at concentrations that don’t match our day to day exposure. We are exposed to a cocktail of chemicals, which in combination, may have enhanced harmful effects.

Several studies support a link between a high fat diet and breast cancer, although this link is still debated, as what lies behind this effect is unclear. A high fat diet may not on its own be a serious contributor to breast cancer but its effect may be enhanced by the presence of EDCs in our bodies. The current project aims to address this knowledge gap. It will investigate the impact of complex mixtures of EDCs and saturated fatty acids (as found in a high fat diet) on breast tissue development and growth and initiation of breast cancer.

Dr Silva’s research will use an innovative “Breast-on-Chip” methodology developed at Brunel University. Different breast cell types are grown together in 3D cell culture and are fed with a constant flow of media and nutrients. This system is designed to mimic the physical environment of breast tissue. The approach provides a more robust and representative alternative to current laboratory and animal-based methods.

The EDCs to be tested include bisphenol A (plastic component), PBDEs (flame retardants), parabens (preservatives), benzophenones (UV filters), DDT (pesticide), polychlorinated biphenyls (used in hydraulic fluids, now banned) and galaxolide (perfume). The three most common fatty acids (lauric, palmitic and steric acids) and EDCs will be tested at concentrations that have been measured previously in human breast tissue.

The research aims to understand the impact of combinations of chemical exposures and lifestyle factors on early stages of breast carcinogenesis. This will provide a framework for further public information and practical advice on ways to reduce exposure to factors that contribute to breast cancer risk.

Previous funding: This is Dr Silva’s second BCUK grant. Her previous work investigated effects of low-dose mixtures of EDCs on breast cancer initiation using 3D breast cell culture. She found that low concentrations of 4 EDCs (propylparaben, BPA, DDT and benzophenone-3) added to breast cells grown in 3D cell culture caused changes resembling early stage breast cancer. When EDC mixtures were used, changes were more significant. Her new project uses a more sophisticated 3D model to examine the effects of EDCs in combination with saturated fatty acids