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cc-by (c) Hendricks, Linda A.J. et al., 2025
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223521

The risk of a second primary cancer in PTEN Hamartoma Tumor Syndrome (PHTS)

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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. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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HENDRICKS, Linda A.J., et al. The risk of a second primary cancer in PTEN Hamartoma Tumor Syndrome (PHTS). Genetics in Medicine. 2025. Vol. 27, num. 10, pags. 101467. ISSN 1530‑0366. [consulted: 12 of August of 2026]. Available at: https://hdl.handle.net/2445/223521

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