Sistema de Salut de Catalunya
Institut Català de la Salut
[Hendricks LAJ, Verbeek KCJ] Department of Human Genetics, Radboudumc expert center for PHTS, Radboud university medical center, Nijmegen, The Netherlands. Radboud university medical center, Radboud Institute for Medical Innovation, Nijmegen, The Netherlands. [Schuurs-Hoeijmakers JHM] Department of Human Genetics, Radboudumc expert center for PHTS, Radboud university medical center, Nijmegen, The Netherlands. [de Jong MM] Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. [Links TP] Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. [Brems H] Center for Human Genetics, University Hospital Leuven, University of Leuven, Leuven, Belgium. [Balmaña J, Torres M] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-11-03T08:28:00Z
2025-11-03T08:28:00Z
2025-10
PTEN hamartoma tumor syndrome; Hereditary cancer; Second primary cancer risk
Síndrome de tumor hamartoma PTEN; Cáncer hereditario; Riesgo de segundo cáncer primario
Síndrome de tumor hamartoma PTEN; Càncer hereditari; Risc de segon càncer primari
Purpose Patients with PTEN Hamartoma Tumor Syndrome (PHTS) have high hereditary cancer risks for breast, endometrial, and thyroid cancer. Patients develop multiple primary cancers, but these risks remain uncertain. We aimed to provide the second primary cancer risk. Methods This European cohort study assessed second primary cancer risks with Kaplan-Meier analyses using data from medical files, registries and/or patient questionnaires. Results Overall, 279 adult PHTS patients with (a history of) cancer were included (80% female). Among females, 106 (54%) developed a PHTS-related second primary cancer after a PHTS-related first primary cancer, whereas 10 (29%) males developed a PHTS-related second primary cancer after a PHTS-related first primary cancer. The 5- and 10-year PHTS-related second primary cancer risks were 24.5% (95% CI = 18.1-32.5) and 45.7% (95% CI = 36.9-55.4) in females and 14.5% (95% CI = 5.7-34.1) and 19.8% (95% CI = 8.6-41.9) in males, respectively. Furthermore, 5- and 10-year risks for a second primary breast cancer after a first primary breast cancer were 23.3% (95% CI = 14.9-35.2) and 45.6% (95% CI = 33.0-60.2) in females, respectively. Conclusion This study demonstrated that PHTS patients have high second primary cancer risks, which is driven by breast cancer in females. Hence, identifying patients with PHTS before or at first primary cancer diagnosis is essential to enable potential early detection or prevention of a second primary cancer through surveillance or risk-reducing surgery.
This work has been funded, in part, by the PTEN Research Foundation, a charity governed by English law (charity number 117358) to L.A.J.H. and J.R.V. under grant number RUM 17-002 and the European Union under Horizon Europe to K.C.J.V. under grant number 101095483.
Article
Published version
English
Càncer - Aspectes genètics; Cèl·lules - Proliferació; Càncer - Factors de risc; DISEASES::Neoplasms::Neoplasms, Second Primary; CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::PTEN Phosphohydrolase; DISEASES::Neoplasms::Hamartoma::Hamartoma Syndrome, Multiple; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors; DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease; ENFERMEDADES::neoplasias::neoplasias primarias secundarias; COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::hidrolasas::esterasas::monoéster fosfórico hidrolasas::PTEN fosfohidrolasa; ENFERMEDADES::neoplasias::hamartoma::síndrome de hamartomas múltiples; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo; ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::susceptibilidad a enfermedades::predisposición genética a la enfermedad
Elsevier
Genetics in Medicine;27(10)
https://doi.org/10.1016/j.gim.2025.101467
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3396]
