From treatment to prevention
Investigating the relationship between a stromal wound healing phenotype and breast density
Around one in eight women will develop breast cancer, and despite survival doubling in the past 40 years, more than 11,000 women die from breast cancer every year in the UK. To reduce breast cancer mortalities, it is essential that this disease is detected at an earlier stage where it is more treatable. To shift towards prevention and earlier detection, research needs to focus on underlying cancer drivers, mechanisms, and risks.
Women with high density breasts (>75%) have a 4 to 6 fold increased risk of breast cancer compared to those with low density breasts (<5%). Breast stroma has been shown to be a different composition in high density breasts, particularly in terms of collagen. Collagen is produced by fibroblasts which are critical in wound healing and more active in high density breasts, and breast cancer resembles a non-healing wound. It is hypothesised that activated fibroblasts that increase breast density are creating a wound-like environment. This may help cancer to develop and the precancerous condition, ductal carcinoma in-situ (DCIS) to become invasive.
Hadiyat Ogunlayi, an MB-PhD student from The University of Manchester is investigating the relationship between a stromal wound healing phenotype and breast density as a mechanism for breast cancer development. As such, her project will investigate the relationship between breast density, wound healing, DCIS and cancer.
I didn’t know it would be possible for me to do a PhD as part of my overall medical training, and I feel extremely happy. For me, a career as a clinician and a cancer researcher is the ultimate combination to really making a difference in patients’ lives.
MBPhD student at The University of Manchester
Hadiyat began her undergraduate studies at The University of Bristol in 2012 in Biochemistry which she followed with a Master’s in Biomedical Sciences Research. After this, she began her medical degree at The University of Manchester and upon completing her third year of medicine, Hadiyat enrolled on the MB-PhD programme in 2020, which is funded by Cancer Research UK through the Clinical Academic Training Grant. She is now working within Professor Cliona Kirwan’s group in the Division of Cancer Sciences.
Hadiyat’s research is focused on investigating the relationship between a stromal wound healing phenotype and breast density. This study utilises the Manchester Cancer Research Centre Biobank to provide residual breast tissue samples from patients undergoing therapeutic mastectomies at Wythenshawe Hospital. Fibroblasts are being grown ex vivo from the breast cancer and DCIS tissue samples and their corresponding normal breast tissue samples. She will compare the wound-like behaviours of different fibroblasts to see whether the procoagulant fibroblasts promote cancer-like behaviour in ER+, Triple negative, DCIS and normal breast cell lines.
Hadiyat will also go on to test whether anti-clotting drugs can inhibit the progression of DCIS to invasive breast cancer. She will also investigate how coagulation relates to inflammation in the tumour environment. Findings from these experiments hope to identify predictive markers of breast cancer along with potential therapies to improve treatment of breast cancer.
I feel like this is such a great opportunity and I feel so privileged to be involved in this training. I felt like I had to choose between medicine and research at the time and to be able to do both is amazing.
Manchester is uniquely placed to investigate the behaviour of live human fibroblasts from breast tissue due the expertise of the breast cancer researchers at the Manchester breast centre. As a Consultant Breast Cancer Surgeon, Professor Cliona Kirwan is an ideal supervisor to inform and guide research activities within this project. Additionally, Dr Anne Armstrong, a Consultant in Medical Oncology at The Christie provides a clinical outlook to guide research questions from a patient’s perspective. Professor Rob Clarke who is the director of the Manchester Breast Centre and the head of the Breast Biology Group, is the ideal supervisor for providing significant guidance especially with regards to the experimental work. In addition to supervisory guidance, the other researchers within the breast biology laboratory including John Castle who is Professor Kirwan’s Research associate, provide significant input and guidance to further help with answering the research questions. This team science facilitates the translational aspects of this work and means that research can be approached from multiple angles.
I’ve felt very at home in Manchester. Everyone is just so friendly and caring and the people I have met within the faculty have been very down to earth and approachable. It’s a very warm environment and I cannot recommend it enough for both the great environment and the highly skilled and experienced research teams here.
Post MB-PhD aspirations
Hadiyat hopes that by the time she has completed her MB-PhD she will have analysed the samples from up to 60 patients. She would like to go on to publish a paper from her findings before she then returns to her medical degree.
In the future, Hadiyat would like to work as a clinician and specialise in oncology. For now, however, she wants to continue working in cancer research alongside her training and see what research opportunities come her way.
Advice to those wanting to do an MBPhD
“PhDs are tough and there will be times when your experiments are not going to work, you have to redo the experiment over and over again. You have to be resilient and you have to be patient and also be passionate about the work you’re doing so that you can keep going,” Hadiyat said.
Focus on the positives when things don’t work out and keep pushing yourself to keep going and take mental health breaks, so you don’t work yourself into the ground.