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

Abstract

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.