Patients with PTEN hamartoma tumor syndrome (PHTS, comprising Cowden, Bannayan‐Riley‐Ruvalcaba, and Proteus‐like syndromes) are at increased risk of developing cancer due to pathogenic PTEN germline variants. This review summarizes age‐, sex‐, and type‐specific malignant cancer risks for PHTS patients, which is urgently needed for clinical management. A PubMed literature search for Standardized Incidence Ratios or Cumulative Lifetime cancer risks (CLTRs) resulted in nine cohort studies comprising four independent PHTS cohorts, including mainly index cases and prevalent cancer cases. The median age at diagnosis was 36 years. Reported CLTRs for any cancer varied from 81% to 90%. The tumor spectrum included female breast cancer (CLTRs including sex‐specific estimates at age 60‐70: 67% to 85%), endometrium cancer (19% to 28%), thyroid cancer (6% to 38%), renal cancer (2% to 24%), colorectal cancer (9% to 32%), and melanoma (0% to 6%). Although these estimates provide guidance for clinical care, discrepancies between studies, sample sizes, retrospective designs, strongly ascertained cases, and lack of pediatric research emphasizes that data should be interpreted with great caution. Therefore, more accurate and more personalized age‐, sex‐, and cancer‐specific risk estimates are needed to enable counseling of all PHTS patients irrespective of ascertainment, and improvement of cancer surveillance guidelines.

中文翻译：

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PTEN错构瘤肿瘤综合征与年龄相关的癌症风险综述

PTEN 错构瘤肿瘤综合征（PHTS，包括 Cowden、Bannayan-Riley-Ruvalcaba 和 Proteus 样综合征）患者因致病性PTEN患癌症的风险增加种系变体。本综述总结了临床管理急需的 PHTS 患者的年龄、性别和类型特异性恶性肿瘤风险。对标准化发病率或累积终生癌症风险 (CLTR) 的 PubMed 文献搜索产生了九个队列研究，包括四个独立的 PHTS 队列，主要包括指示病例和流行癌症病例。诊断时的中位年龄为 36 岁。报告的任何癌症的 CLTR 从 81% 到 90% 不等。肿瘤谱包括女性乳腺癌（CLTR，包括 60-70 岁性别特异性估计：67% 至 85%）、子宫内膜癌（19% 至 28%）、甲状腺癌（6% 至 38%）、肾癌（ 2% 至 24%）、结直肠癌（9% 至 32%）和黑色素瘤（0% 至 6%）。尽管这些估计为临床护理提供了指导，但研究之间的差异，样本量、回顾性设计、强有力的病例和缺乏儿科研究都强调应该非常谨慎地解释数据。因此，需要更准确和更个性化的年龄、性别和癌症特定风险估计，以便为所有 PHTS 患者提供咨询，而不管确定和改进癌症监测指南。