Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study

Linda A J Hendricks; Katja C J Verbeek; Janneke H M Schuurs-Hoeijmakers; Robin de Putter; Arvīds Irmejs; Hilde Brems; Sien H Van Daele; Violetta C Anastasiadou; Lenka Foretová; Patrick R Benusiglio; Anna Gerasimenko; Chrystelle Colas; Marie-Charlotte Villy; Claude Houdayer; Maud Branchaud; Robert Hüneburg; Stefan Aretz; Arne Jahn; Verena Steinke-Lange; Giovanni Innella; Daniela Turchetti; Valeria Barili; Maurizio Genuardi; Arianna Panfili; Margherita Baldassarri; Mirjam M de Jong; Thera P Links; Edward M Leter; Daniëlle G M Bosch; Stephany H Donze; Rachel S van der Post; Arjen R Mensenkamp; Harm Westdorp; Hildegunn Høberg-Vetti; Marianne Tveit Haavind; Kjersti Jørgensen; Lovise Mæhle; Siri Briskemyr; Juliette Dupont Garcia; Ana Blatnik; Judith Balmaña; Maite Torres; Joan Brunet; Roser Lleuger-Pujol; Emma Tham; Marc Tischkowitz; D Gareth Evans; Zerin Hyder; Nicoline Hoogerbrugge; Janet R Vos

doi:10.1038/s44276-025-00157-y

Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study

Linda A J Hendricks, Katja C J Verbeek, Janneke H M Schuurs-Hoeijmakers, Robin de Putter, Arvīds Irmejs, Hilde Brems, Sien H Van Daele, Violetta C Anastasiadou, Lenka Foretová, Patrick R Benusiglio, Anna Gerasimenko, Chrystelle Colas, Marie-Charlotte Villy, Claude Houdayer, Maud Branchaud, Robert Hüneburg, Stefan Aretz, Arne Jahn, Verena Steinke-Lange, Giovanni InnellaDaniela Turchetti, Valeria Barili, Maurizio Genuardi, Arianna Panfili, Margherita Baldassarri, Mirjam M de Jong, Thera P Links, Edward M Leter, Daniëlle G M Bosch, Stephany H Donze, Rachel S van der Post, Arjen R Mensenkamp, Harm Westdorp, Hildegunn Høberg-Vetti, Marianne Tveit Haavind, Kjersti Jørgensen, Lovise Mæhle, Siri Briskemyr, Juliette Dupont Garcia, Ana Blatnik, Judith Balmaña, Maite Torres, Joan Brunet, Roser Lleuger-Pujol, Emma Tham, Marc Tischkowitz, D Gareth Evans, Zerin Hyder, Nicoline Hoogerbrugge, Janet R Vos (Corresponding Author)

Institute of Oncology and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) patients have a high hereditary risk of cancer, especially breast (BC), endometrial (EC), and thyroid cancer (TC). However, the prognosis of PHTS-related cancers is unknown.

METHODS: This European cohort study included adult PHTS patients with data from medical files, registries, and/or questionnaires. Overall survival (OS) was assessed using Kaplan-Meier analyses and were compared with sporadic cancer and the general population using standardized mortality (SMR) and relative survival rates (RSR). Survival bias was addressed using left-truncation.

RESULTS: Overall, 147 BC patients were included. The 10y-OS was 77% (95%CI = 66-90), decreasing with increasing stage from 90% (95%CI = 73-100) for stage 0 to 0% (95%CI = 0-0) for stage IV. BC relative survival was comparable to sporadic BC in the first two years (2y-RSR = 1.1; 95%CI = 1.1-1.1) and increasing thereafter (5y-RSR = 1.7; 95%CI = 1.6-1.7). For TC (N = 56) and EC (N = 35), 10y-OS was 87% (95%CI = 74-100) and 64% (95%CI = 38-100), respectively. Overall and cancer-specific mortality in female PHTS patients exceeded general population rates (SMR = 3.7; 95%CI = 2.6-5.0 and SMR = 2.7; 95%CI = 1.6-4.4).

CONCLUSIONS: The prognosis of PHTS-related cancers was comparable to the general population. The higher overall mortality in PHTS patients is presumably related to their higher cancer incidence. These findings, and the high survival observed in early-stage cancer, emphasise the importance of recognising PHTS early to facilitate cancer surveillance.

Original language	English
Pages (from-to)	42
Number of pages	10
Journal	BJC reports
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s44276-025-00157-y
Publication status	Published - 4 Jun 2025

Field of Science*

3.2 Clinical medicine

Publication Type*

1.3. Anonymously reviewed scientific article published in a journal with an international editorial board and is available in another indexed database

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s44276-025-00157-y

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Hendricks, L. A. J., Verbeek, K. C. J., Schuurs-Hoeijmakers, J. H. M., de Putter, R., Irmejs, A., Brems, H., Van Daele, S. H., Anastasiadou, V. C., Foretová, L., Benusiglio, P. R., Gerasimenko, A., Colas, C., Villy, M.-C., Houdayer, C., Branchaud, M., Hüneburg, R., Aretz, S., Jahn, A., Steinke-Lange, V., ... Vos, J. R. (2025). Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study. BJC reports, 3(1), 42. https://doi.org/10.1038/s44276-025-00157-y

@article{7165123eccdd49258f66b36e69377442,

title = "Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study",

abstract = "BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) patients have a high hereditary risk of cancer, especially breast (BC), endometrial (EC), and thyroid cancer (TC). However, the prognosis of PHTS-related cancers is unknown.METHODS: This European cohort study included adult PHTS patients with data from medical files, registries, and/or questionnaires. Overall survival (OS) was assessed using Kaplan-Meier analyses and were compared with sporadic cancer and the general population using standardized mortality (SMR) and relative survival rates (RSR). Survival bias was addressed using left-truncation.RESULTS: Overall, 147 BC patients were included. The 10y-OS was 77% (95%CI = 66-90), decreasing with increasing stage from 90% (95%CI = 73-100) for stage 0 to 0% (95%CI = 0-0) for stage IV. BC relative survival was comparable to sporadic BC in the first two years (2y-RSR = 1.1; 95%CI = 1.1-1.1) and increasing thereafter (5y-RSR = 1.7; 95%CI = 1.6-1.7). For TC (N = 56) and EC (N = 35), 10y-OS was 87% (95%CI = 74-100) and 64% (95%CI = 38-100), respectively. Overall and cancer-specific mortality in female PHTS patients exceeded general population rates (SMR = 3.7; 95%CI = 2.6-5.0 and SMR = 2.7; 95%CI = 1.6-4.4).CONCLUSIONS: The prognosis of PHTS-related cancers was comparable to the general population. The higher overall mortality in PHTS patients is presumably related to their higher cancer incidence. These findings, and the high survival observed in early-stage cancer, emphasise the importance of recognising PHTS early to facilitate cancer surveillance.",

author = "Hendricks, {Linda A J} and Verbeek, {Katja C J} and Schuurs-Hoeijmakers, {Janneke H M} and {de Putter}, Robin and Arvīds Irmejs and Hilde Brems and {Van Daele}, {Sien H} and Anastasiadou, {Violetta C} and Lenka Foretov{\'a} and Benusiglio, {Patrick R} and Anna Gerasimenko and Chrystelle Colas and Marie-Charlotte Villy and Claude Houdayer and Maud Branchaud and Robert H{\"u}neburg and Stefan Aretz and Arne Jahn and Verena Steinke-Lange and Giovanni Innella and Daniela Turchetti and Valeria Barili and Maurizio Genuardi and Arianna Panfili and Margherita Baldassarri and {de Jong}, {Mirjam M} and Links, {Thera P} and Leter, {Edward M} and Bosch, {Dani{\"e}lle G M} and Donze, {Stephany H} and {van der Post}, {Rachel S} and Mensenkamp, {Arjen R} and Harm Westdorp and Hildegunn H{\o}berg-Vetti and {Tveit Haavind}, Marianne and Kjersti J{\o}rgensen and Lovise M{\ae}hle and Siri Briskemyr and Garcia, {Juliette Dupont} and Ana Blatnik and Judith Balma{\~n}a and Maite Torres and Joan Brunet and Roser Lleuger-Pujol and Emma Tham and Marc Tischkowitz and Evans, {D Gareth} and Zerin Hyder and Nicoline Hoogerbrugge and Vos, {Janet R}",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

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doi = "10.1038/s44276-025-00157-y",

language = "English",

volume = "3",

pages = "42",

journal = "BJC reports",

issn = "2731-9377",

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Hendricks, LAJ, Verbeek, KCJ, Schuurs-Hoeijmakers, JHM, de Putter, R, Irmejs, A, Brems, H, Van Daele, SH, Anastasiadou, VC, Foretová, L, Benusiglio, PR, Gerasimenko, A, Colas, C, Villy, M-C, Houdayer, C, Branchaud, M, Hüneburg, R, Aretz, S, Jahn, A, Steinke-Lange, V, Innella, G, Turchetti, D, Barili, V, Genuardi, M, Panfili, A, Baldassarri, M, de Jong, MM, Links, TP, Leter, EM, Bosch, DGM, Donze, SH, van der Post, RS, Mensenkamp, AR, Westdorp, H, Høberg-Vetti, H, Tveit Haavind, M, Jørgensen, K, Mæhle, L, Briskemyr, S, Garcia, JD, Blatnik, A, Balmaña, J, Torres, M, Brunet, J, Lleuger-Pujol, R, Tham, E, Tischkowitz, M, Evans, DG, Hyder, Z, Hoogerbrugge, N & Vos, JR 2025, 'Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study', BJC reports, vol. 3, no. 1, pp. 42. https://doi.org/10.1038/s44276-025-00157-y

TY - JOUR

T1 - Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study

AU - Hendricks, Linda A J

AU - Verbeek, Katja C J

AU - Schuurs-Hoeijmakers, Janneke H M

AU - de Putter, Robin

AU - Irmejs, Arvīds

AU - Brems, Hilde

AU - Van Daele, Sien H

AU - Anastasiadou, Violetta C

AU - Foretová, Lenka

AU - Benusiglio, Patrick R

AU - Gerasimenko, Anna

AU - Colas, Chrystelle

AU - Villy, Marie-Charlotte

AU - Houdayer, Claude

AU - Branchaud, Maud

AU - Hüneburg, Robert

AU - Aretz, Stefan

AU - Jahn, Arne

AU - Steinke-Lange, Verena

AU - Innella, Giovanni

AU - Turchetti, Daniela

AU - Barili, Valeria

AU - Genuardi, Maurizio

AU - Panfili, Arianna

AU - Baldassarri, Margherita

AU - de Jong, Mirjam M

AU - Links, Thera P

AU - Leter, Edward M

AU - Bosch, Daniëlle G M

AU - Donze, Stephany H

AU - van der Post, Rachel S

AU - Mensenkamp, Arjen R

AU - Westdorp, Harm

AU - Høberg-Vetti, Hildegunn

AU - Tveit Haavind, Marianne

AU - Jørgensen, Kjersti

AU - Mæhle, Lovise

AU - Briskemyr, Siri

AU - Garcia, Juliette Dupont

AU - Blatnik, Ana

AU - Balmaña, Judith

AU - Torres, Maite

AU - Brunet, Joan

AU - Lleuger-Pujol, Roser

AU - Tham, Emma

AU - Tischkowitz, Marc

AU - Evans, D Gareth

AU - Hyder, Zerin

AU - Hoogerbrugge, Nicoline

AU - Vos, Janet R

PY - 2025/6/4

Y1 - 2025/6/4

N2 - BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) patients have a high hereditary risk of cancer, especially breast (BC), endometrial (EC), and thyroid cancer (TC). However, the prognosis of PHTS-related cancers is unknown.METHODS: This European cohort study included adult PHTS patients with data from medical files, registries, and/or questionnaires. Overall survival (OS) was assessed using Kaplan-Meier analyses and were compared with sporadic cancer and the general population using standardized mortality (SMR) and relative survival rates (RSR). Survival bias was addressed using left-truncation.RESULTS: Overall, 147 BC patients were included. The 10y-OS was 77% (95%CI = 66-90), decreasing with increasing stage from 90% (95%CI = 73-100) for stage 0 to 0% (95%CI = 0-0) for stage IV. BC relative survival was comparable to sporadic BC in the first two years (2y-RSR = 1.1; 95%CI = 1.1-1.1) and increasing thereafter (5y-RSR = 1.7; 95%CI = 1.6-1.7). For TC (N = 56) and EC (N = 35), 10y-OS was 87% (95%CI = 74-100) and 64% (95%CI = 38-100), respectively. Overall and cancer-specific mortality in female PHTS patients exceeded general population rates (SMR = 3.7; 95%CI = 2.6-5.0 and SMR = 2.7; 95%CI = 1.6-4.4).CONCLUSIONS: The prognosis of PHTS-related cancers was comparable to the general population. The higher overall mortality in PHTS patients is presumably related to their higher cancer incidence. These findings, and the high survival observed in early-stage cancer, emphasise the importance of recognising PHTS early to facilitate cancer surveillance.

AB - BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) patients have a high hereditary risk of cancer, especially breast (BC), endometrial (EC), and thyroid cancer (TC). However, the prognosis of PHTS-related cancers is unknown.METHODS: This European cohort study included adult PHTS patients with data from medical files, registries, and/or questionnaires. Overall survival (OS) was assessed using Kaplan-Meier analyses and were compared with sporadic cancer and the general population using standardized mortality (SMR) and relative survival rates (RSR). Survival bias was addressed using left-truncation.RESULTS: Overall, 147 BC patients were included. The 10y-OS was 77% (95%CI = 66-90), decreasing with increasing stage from 90% (95%CI = 73-100) for stage 0 to 0% (95%CI = 0-0) for stage IV. BC relative survival was comparable to sporadic BC in the first two years (2y-RSR = 1.1; 95%CI = 1.1-1.1) and increasing thereafter (5y-RSR = 1.7; 95%CI = 1.6-1.7). For TC (N = 56) and EC (N = 35), 10y-OS was 87% (95%CI = 74-100) and 64% (95%CI = 38-100), respectively. Overall and cancer-specific mortality in female PHTS patients exceeded general population rates (SMR = 3.7; 95%CI = 2.6-5.0 and SMR = 2.7; 95%CI = 1.6-4.4).CONCLUSIONS: The prognosis of PHTS-related cancers was comparable to the general population. The higher overall mortality in PHTS patients is presumably related to their higher cancer incidence. These findings, and the high survival observed in early-stage cancer, emphasise the importance of recognising PHTS early to facilitate cancer surveillance.

UR - https://pubmed.ncbi.nlm.nih.gov/40468016/

U2 - 10.1038/s44276-025-00157-y

DO - 10.1038/s44276-025-00157-y

M3 - Article

C2 - 40468016

SN - 2731-9377

VL - 3

SP - 42

JO - BJC reports

JF - BJC reports

IS - 1

ER -

Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study

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