Understanding factors that influence breast cancer risk, disease progression and treatment outcomes
Lead Research Organisation:
University of Bath
Department Name: Department for Health
Abstract
BACKGROUND
Breast cancer is the most common cancer for females in the UK, with approximately 55,000 new cases each year. Being overweight, obese, or physically inactive increases the risk of developing this prevalent disease, and although the mechanisms are not well established, it is likely that impaired anti-cancer immunity and inflammatory processes in adipose tissue have a role. For women who have developed breast cancer, a common form of treatment is neoadjuvant chemotherapy, which is administered for several months prior to surgery. Initial evidence shows that measurements of anti-cancer immunity and tumour activity, the latter through cell-free circulating tumour DNA analysis, predicts successful breast cancer treatment outcomes. It is likely that lifestyle factors, such as cardiorespiratory fitness and body composition, which also influence the success of cancer therapy, interact, but these measurements have not been assessed in parallel.
AIMS AND OBJECTIVES
This work will assess multiple factors, which are known to influence disease risk and treatment outcomes, both in healthy people and patients diagnosed with breast cancer. Investigations will combine immunological and genetic laboratory methodology (i.e. anti-cancer immunity and cell-free circulating tumour DNA in serum) with objective methodology for precisely assessing lifestyle (e.g. physical activity level, cardiorespiratory fitness, body composition). Investigations will probe mechanistic processes that drive tumour progression, including adipose tissue inflammation, and will investigate whether lifestyle interventions can modulate these processes.
POTENTIAL APPLICATIONS AND BENEFITS/ RELEVANCE TO THE MEDICAL RESEARCH COUNCIL (MRC)
This research will improve our understanding of biological processes that influence the risk of developing breast cancer and contribute towards disease progression. Importantly, in healthy people, this work will stablish whether this processes can be modified by lifestyle interventions that could be recommended to reduce cancer risk. In addition, factors predicting treatment outcomes may be stablished and validated, which could be incorporated into routine clinical practice.
This research fits well within the MRC strategic plan 2014-2019, which aims at setting research priorities which are most likely to deliver improved health outcomes. For example, under research priority theme one (resilience, repair and replacement) this work provides insight into our natural protection against cancer, improving understanding of how resilience to disease breaks down and how it may be repaired with interventions that improve disease processes. In addition, under research priority theme two (living a long and healthy life), this work will provide information about lifestyles affecting health, informing the development of effective strategies for promoting healthy behaviour and tackling lifestyles that lead to disease.
Breast cancer is the most common cancer for females in the UK, with approximately 55,000 new cases each year. Being overweight, obese, or physically inactive increases the risk of developing this prevalent disease, and although the mechanisms are not well established, it is likely that impaired anti-cancer immunity and inflammatory processes in adipose tissue have a role. For women who have developed breast cancer, a common form of treatment is neoadjuvant chemotherapy, which is administered for several months prior to surgery. Initial evidence shows that measurements of anti-cancer immunity and tumour activity, the latter through cell-free circulating tumour DNA analysis, predicts successful breast cancer treatment outcomes. It is likely that lifestyle factors, such as cardiorespiratory fitness and body composition, which also influence the success of cancer therapy, interact, but these measurements have not been assessed in parallel.
AIMS AND OBJECTIVES
This work will assess multiple factors, which are known to influence disease risk and treatment outcomes, both in healthy people and patients diagnosed with breast cancer. Investigations will combine immunological and genetic laboratory methodology (i.e. anti-cancer immunity and cell-free circulating tumour DNA in serum) with objective methodology for precisely assessing lifestyle (e.g. physical activity level, cardiorespiratory fitness, body composition). Investigations will probe mechanistic processes that drive tumour progression, including adipose tissue inflammation, and will investigate whether lifestyle interventions can modulate these processes.
POTENTIAL APPLICATIONS AND BENEFITS/ RELEVANCE TO THE MEDICAL RESEARCH COUNCIL (MRC)
This research will improve our understanding of biological processes that influence the risk of developing breast cancer and contribute towards disease progression. Importantly, in healthy people, this work will stablish whether this processes can be modified by lifestyle interventions that could be recommended to reduce cancer risk. In addition, factors predicting treatment outcomes may be stablished and validated, which could be incorporated into routine clinical practice.
This research fits well within the MRC strategic plan 2014-2019, which aims at setting research priorities which are most likely to deliver improved health outcomes. For example, under research priority theme one (resilience, repair and replacement) this work provides insight into our natural protection against cancer, improving understanding of how resilience to disease breaks down and how it may be repaired with interventions that improve disease processes. In addition, under research priority theme two (living a long and healthy life), this work will provide information about lifestyles affecting health, informing the development of effective strategies for promoting healthy behaviour and tackling lifestyles that lead to disease.
| Description | Collaborative project with the University of Sao Paulo (Brazil) via the Flexible Funding Award from the GW4 Biomed MRC DTP |
| Organisation | Universidade de São Paulo |
| Country | Brazil |
| Sector | Academic/University |
| PI Contribution | This collaboration was already set up by my main supervisor of my PhD, Dr James Turner, who met Professor Patricia Brum and her research team in 2015 when a University of Bath delegation visited the University of Sao Paulo. Since then, Dr Turner has subsequently visited Brazil to establish and contribute to research projects being conducted in Professor Brum's laboratory, they have jointly published a review article together (Turner & Brum 2017 Oxid Med Cll Longev) on the theme of exercise, immunological ageing and cancer, and have received funding from the Sao Paulo research foundation FAPESP to support their collaboration. I contributed towards two of their projects thanks to being granted the Flexible Funding award from the GW4 MRC DTP, which allowed me to go to the University of Sao Paulo on a collaborative visit for 5 weeks (30 Sept- 04 Nov 2019). As part of these projects I made immunological measurements in cryopreserved peripheral blood mononuclear cells, comparing breast cancer survivors before and after a lifestyle intervention, and also comparing lung cancer patients to healthy controls. Dr James Turner provided some of the reagents and items needed for these immunological analyses and his expertise in immunology and lifestyle in the context of cancer. I also have a background in cancer cell biology and health, which I applied to these projects. I am currently analysing the data, creating the graphs, conducting statistical analyses and writing the manuscript, with Dr Turner's guidance. |
| Collaborator Contribution | Professor Patricia Brum's research focuses on the benefits of exercise training for patients with cardiovascular disease or cancer, examining cellular and molecular mechanisms of disease and treatment. Her and her research team designed the project, recruited the participants, took measurements of lifestyle and collected blood samples for measurements of health and to isolate cryopreserved peripheral blood mononuclear cells (PBMCs) before and after the intervention. Those measurements of health are being included in our statistical analyses for the immunological data. Professor Brum provided with the laboratory space for me to perform the immunological assays, the equipment and some of the reagents, as well as her expertise and support, from her and from members of her research team. The project involves different waves, and it has been paused due to the pandemic. There are plans for another wave of breast cancer survivors to be recruited for the training intervention, as well as to increase the sample size of the lung cancer patients and healthy controls, whenever it is possible to resume these research activities. It is likely that I will then visit their laboratories again to analyse those extra cryopreserved samples, but dates are currently uncertain. This extra data would be added to the existing one and contribute towards the publication and the thesis chapter |
| Impact | The projects undertaken as part of this collaboration extend the investigations of lifestyle and immunity (which are being carried out with breast cancer patients) as part of my PhD in Bath into patients who have finished their treatment for breast cancer. The main outcomes of this collaborative visit are the findings derived from the immunological analyses I performed on those samples collected by our collaborators in Brazil. A research article and a thesis chapter for my PhD will be produced based on this work. These investigations contribute towards understanding the biological processes involved in tumour progression/ regression and the influence of exercise on treatment outcomes, survival and overall health. They enhance our understanding of each of the steps of the disease and provide with evidence that may contribute towards improving patient care. Finally, this collaborative visit has strengthened the international bonds of our research team and widened my professional network. |
| Start Year | 2015 |
| Description | Presentation at the 3TM (Three Minutes Thesis) competition final in Bath |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | I was finalist in the 3MT (Three Minutes Thesis) competition organised by the University of Bath, which took place at the Bath Royal Literary and Scientific Institute in Bath on the 4th June 2019. It was a free event, open to the general public, and a mixed audience attended ( lecturers, postgraduate students and undergraduate students across the different departments of the University, as well as members of the general public, relatives, etc). In summary, I delivered a three minutes presentation about the different projects I am involved in as part of my PhD, focusing in lifestyle and immunity in breast cancer, to a non-specialized audience. There was a panel of three judges which made some questions after each presentation, and the audience was also encouraged to make questions, which lead to very interesting discussions about lifestyle and its influence in cancer treatment and outcomes. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentation at the Research objects event, organised by the University of Bath Volunteering Group and the Age UK B&NES (Bath and North East Somerset) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | I delivered a presentation during the event called Research Objects, which is organised yearly by the Volunteering team of the University of Bath in collaboration with Age UK. The event took place on the 31st January 2019, and the aim was to engage older people with science. Therefore, I delivered a 10 minutes presentation about my research (breast cancer and the influence of lifestyle and immunity) to about 10-20 to members of the Age UK B&NES Culture Club (comprised of ages 55 years and over) at St John's Foundation, in Bath. After the presentation, the audience got involved and asked questions, and some of the attendees showed a lot of interest on my research as they could relate to personal experiences or experiences of relatives and people they knew. It was a very rewarding experience where the attendees learned about the importance and influence of lifestyle in diseases such as cancer, and got a flavour of some of the research that is taking place in the community. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.thesubath.com/ents/event/9095/ |