Cancer outcomes in PHTS - following what happens over time
Introduction
People with PHTS have a higher chance of developing some cancers, especially breast, thyroid, womb (endometrial), kidney, bowel (colorectal) cancer, and a type of skin cancer called melanoma. Because of this, doctors recommend regular surveillance, which means planned checks to look for cancer as early as possible.
At present, cancer treatment for people with PHTS is similar to that for individuals with sporadic cancers. Until recently, it was unknown whether the outcome of cancer treatment in individuals with PHTS differed from the general population.
At the moment, there are no proven ways to prevent cancer in PHTS beyond regular monitoring, so researchers are trying to understand more about why cancer is so common in PHTS. The goal is to find early warning signs, or biomarkers, that could help doctors spot cancer sooner in the future.
Project 1 key facts
Project title: Cancer prognosis and treatment of PHTS patients
Type of study: Natural history/translational medicine
Lead researcher: Prof Nicoline Hoogerbrugge
Institution: Radboud University Medical Center, Nijmegen, Netherlands
Project start: January 2020 Completed: September 2025
Project 1 goals
To better understand how common different cancers are in PHTS and how they are treated.
Project 1 overview
For this study, over 500 people with PHTS who were diagnosed with cancer were identified. The prognosis of these individuals was assessed, with a focus on breast and thyroid cancer. Following diagnosis of cancer in an individual, data was collected for each individual on their treatment and the outcome of the treatment and cancer recurrences and metastases.
Outcomes
This project has now been completed.
The key results showed that the prognosis of PHTS-related cancers was no worse than for comparable cancers in the general population (sporadic cancers) and that standard cancer treatment is appropriate for individuals with PHTS with cancer.
The research also showed that lifestyle among individuals with PHTS is important as a healthier lifestyle (higher physical activity, lower alcohol consumption and tobacco smoking) could potentially decrease breast cancer risk in a similar way as for the general population.
The following publications have resulted from work associated with have resulted from work associated with this grant:
- A review on age‐related cancer risks in PTEN hamartoma tumor syndrome
- Catch them if you are aware: PTEN postzygotic mosaicism in clinically suspicious patients with PTEN Hamartoma Tumour Syndrome and literature review
- Cancer risks by sex and variant type in PTEN Hamartoma Tumor Syndrome
- Genotype-phenotype associations in a large PTEN Hamartoma Tumor Syndrome (PHTS) patient cohort
- Lifestyle factors and breast cancer risk in females with PTEN Hamartoma Tumor Syndrome (PHTS)
- Histopathological phenotyping of cancers in PTEN Hamartoma Tumor Syndrome for improved recognition: A single‐center study
- Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumor Syndrome (PHTS) – a European cohort study
- The risk of a second primary cancer in PTEN Hamartoma Tumor Syndrome (PHTS)
Project 2 key facts
Project title: Researching Early Cancer by quantifying ClonE dynamics in individuals with germline PTEN variants (RECCE-PTEN)
Type of study: Basic research
Lead researchers: Dr Raheleh Rahbari1, Dr Joseph Christopher1,2
Institution: 1Wellcome Sanger Institute, 2University of Cambridge
Project start: February 2026 Expected completion: February 2028
Project 2 goals
To improve outcomes for people with PHTS and cancer, it would be important to detect cancer at its earliest stages when treatments are known to be more effective.
This basic research study aims to understand the very earliest genetic signs of cancer in tissue from people with PHTS.
Project 2 overview
Recent advances in technology allow the research team to detect very early genetic changes linked to cancer, even in normal, healthy tissues.
This study will use cutting-edge technology to analyse these early genetic changes in normal tissues of individuals with PHTS to help understand any patterns that lead to increased cancer risk in certain individuals and tissues.
Anticipated outcomes
It is hoped that this basic research study will help us understand why certain tissues in individuals with PHTS are more prone to cancer while other tissues remain unaffected. It will also investigate if it may be possible to detect indications of cancer in a person with PHTS earlier than is possible using current PHTS cancer surveillance based on medical imaging.
This study is the first of many steps to understand more about cancer in PHTS. Further research will be needed before changes to routine practice for PHTS cancer surveillance can be recommended.
The study will also aim to establish a research network for those taking part in the study and start a biobank (a collection of tissue from people with PHTS who have given their consent for the tissue to be collected). The samples in such a biobank could help accelerate future PHTS research.