New research into cause and treatments for triple negative breast cancer

Potential environmental risk factors and new targets for treating an aggressive form of breast cancer have been identified, according to new data presented at the Society for Endocrinology annual conference.

The study suggests that exposure to common chemicals in our everyday environment may increase the risk of developing a difficult to treat type of breast cancer and highlights strategies for new treatment using combination therapy.

Triple negative breast cancer (TNBC) is an aggressive form that particularly affects younger people and makes up 10-20% of all breast cancer diagnoses. Although still curable if caught early, TNBC is resistant to hormone treatments and newer “targeted” therapies, used to treat other types of breast cancer; TNBC is, therefore, treated with surgery, radiotherapy and chemotherapy. There is a need to better understand the biology of TNBC, to help develop new therapies to improve the survival and quality of life for patients with TNBC and also to identify how people might reduce their risk of developing this disease.

Current hormonal therapies used to treat women with another type of breast cancer that is “hormone receptor positive”, target oestrogen and progesterone receptors, two of 48 nuclear receptors (NRs). Many NRs are altered in breast cancer, and are both potential drivers of breast cancer development and possible new therapeutic targets.

Dr. Laura Matthews and Professor Chris Twelves from the University of Leeds, with Professor Valerie Speirs from the University of Aberdeen led a study funded by the charity Breast Cancer UK. They mapped the entire NR superfamily in samples from different types of breast cancer and from normal breast tissue, to identify common alterations in NR activity. This allowed them to predict which drugs or environmental chemicals are more likely to generate the distinct NR profiles associated with TNBC; these include disinfectants, insecticides, dietary fats and industrial pollutants.

Dr. Matthews comments, “Identifying these NR networks, and ways they might be controlled in patients with TNBC is really important. We are now investigating how the environmental chemicals change the behaviour of normal breast cells so we can understand how they might drive cancer development. We are also testing whether using drug combinations that target multiple NRs at the same time might prevent or be an effective treatment for TNBC.”

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Dr Mangesh Thorat, Deputy Director of the Cancer Prevention Trials Unit, Prevention Trials Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, said:

“It is difficult to comment on the limited data presented, and although preliminary data, authors are pursuing an interesting line of investigations.

“They identify a subset of nuclear receptors with altered expression in a particular type of breast cancer, and a further subset of these is associated with outcome (a prognostic biomarker). If validated in other studies, such biomarkers could be clinically useful. As a second line of investigation, they investigated which environmental exposures (common chemicals or drugs) could induce such alteration in expression. This would be useful in designing studies investigating causes of this type of cancer as well as developing new drugs.

“In summary, while this preliminary study does not at the moment have any clinical or public health implications, it identifies new avenues for research into causes of a type of breast cancer (triple negative breast cancer) and the biomarkers identified could be clinically useful in treatment of this cancer if appropriately validated in further studies.”

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