Case Study: Assessing the outcomes of cancer in PHTS

Key facts

Research category: Natural history/translational medicine

Lead researcher: Professor Nicoline Hoogerbrugge, MD PhD

Institution: Radboud University Medical Center, Nijmegen, Netherlands

Project start: January 2020      Expected completion: August 2024

Project goals

Assess the cancer-specific and age-specific prognosis for people with PHTS, and to explore the effect of different cancer treatments on prognosis.


At present cancer treatment of PTEN-mutation carriers is similar to sporadic cancers. However, cancer prognosis in people with PHTS may differ. For example, it has been shown that somatic cancers with PIK3CA mutations and/or somatic PTEN-loss are associated with poorer outcomes in ER positive breast cancer.

Research on treatment outcomes, morbidity and mortality are lacking for PTEN-mutation carriers, and these data may contribute to improved treatment options, outcomes and survival. Recent data show that germline PTEN-mutation carriers may benefit from targeted treatment, such as chemotherapeutic inhibition of PI3K and MAPK pathways, or dose-adapted radiotherapy because of suspected radio-resistance.

Study design

This retrospective study is built upon an earlier project funded by PTEN Research, which established a European PHTS cohort from over 20 centres of PHTS expertise in Europe. The cohort was recruited via the European Reference Network (ERN) GENTURIS, a collaboration amongst expert clinical centres for rare genetic tumour risk syndromes, chaired by Dr Hoogerbrugge.

For this current study, several hundred proven PTEN germline mutation carriers who have been diagnosed with cancer are being identified from the European PHTS cohort. The prognosis of these individuals will be assessed, with a focus on breast and thyroid cancer. Data from after the diagnosis of cancer will be collected on vital status, cancer treatment and surveillance, and cancer recurrences and metastases.

Anticipated outcomes of this work

It is anticipated that this research will result in an improved understanding of the overall, cancer-specific, and disease-free survival rates. Furthermore, it will support more accurate prognosis and survival rate estimation in relation to patient characteristics, tumour characteristics and cancer specific treatment options. Ultimately, it is hoped that this research will contribute to more informed clinical decision making for those managing people with PHTS who develop cancer, resulting in better treatment and improved outcomes.