Investigating the mechanism of Tamoxifen in breast cancer prevention

Closing date: 09/03/2026

MB-PhD Studentship: Investigating the mechanism of Tamoxifen in breast cancer prevention

Lead Supervisors: Dr Andrew Gilmore
Co-Supervisors:
Dr Hannah Harrison, Dr Sacha Howell, Dr Joe Swift

Applications Deadline: Monday 9th March 2026
Interviews: Week commencing 27th April 2026
Start date: September 2026

Project Keywords: Breast cancer prevention, tamoxifen, extracellular matrix
Research Opportunity: MB-PhD Studentship

Project Outline

Breast cancer (BC) is the leading cause of death for UK women under 50. Around 90% of cases are sporadic, raising questions about the aetiology of genomic damage required to initiate BC. The second largest risk factor for BC is high mammographic density (MD), the amount of radiopaque tissue seen on a mammogram. High MD areas are where the collagenous extracellular matrix (ECM) that supports the epithelial ducts is mechanically stiffer. This elevated ECM stiffness in high-risk women is directly linked to their increased breast cancer risk. Furthermore, recent work from our groups has shown that targeting hormone signalling in high-risk women results in significant remodelling of the periductal and perilobular ECM, in particular collagen isoforms that are associated with MD density and stiffness. Thus, BC risk prevention strategies result in changes in breast ECM composition. However, our mechanistic understanding of how drugs like Tamoxifen reduce BC risk is incomplete.

Our current data on the prevention effects of Tamoxifen are from clinical trials where women at high risk provide biopsies prior to and three months after commencing Tamoxifen treatment. We now want to see how Tamoxifen acutely changes breast tissue function to determine how early changes lead to the tissue and ECM remodelling associated with reduced cancer risk. To do this we will utilise a novel breast tissue explant model developed by the applicants. This model maintains ER and PR signalling, along with the full complexity of breast tissue composition, including stromal and immune cells. We will use this model to determine how targeting ER signalling changes breast tissue function and ECM remodelling, utilising our existing multiomic analysis pipelines. This will identify biomarkers for early BC detection and highlight novel targets for prevention.

Applications for this project are now open. Please complete your application on The University of Manchester Postgraduate Application Portal.

About Dr Andrew Gilmore (project Lead Supervisor)

Dr. Andrew Gilmore is a senior lecturer in the Division of Cancer Sciences and is affiliated with Manchester Cell Matrix Centre and Manchester Breast Centre. He obtained his first degree in Zoology and PhD in Biochemistry. Following postdoctoral work at the University of North Carolina he returned to the UK and set up his lab in Manchester.  

The focus of his laboratory is how the extracellular matrix microenvironment of breast tissue alters epithelial cell behaviour to promote cancer initiation. For this they have been using both 3-dimensional cell culture models and studies of clinical trials, in collaboration with breast oncologists.  The overall goal is that by better understanding how breast cancer is promoted they can devise prevention strategies. 

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Andrew Gilmore headshot

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