Genetic tumor syndromes in female cancer - insights into inherited cancer predisposition and clinical implications

Sep 22, 2026

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A relevant proportion of malignancies predominantly or exclusively affecting women, including breast and gynecologic cancers, is attributable to hereditary tumor syndromes, profoundly impacting cancer risk, prognosis, and therapeutic management. Routine comprehensive germline panels extend beyond BRCA1/2 variants to numerous high- and moderate-risk genes, shaping diagnosis and care. Hereditary syndromes such as HBOC, Li-Fraumeni, Lynch, and DICER1 enable specialized surveillance, preventive strategies, and targeted treatment options, requiring interdisciplinary genetic counseling and coordinated clinical management.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Introduction

Archives of Gynecology and Obstetrics (2026) 313:38 [https://doi.org/10.1007/s00404-025-08270-6](https://doi.org/10.1007/s00404-025-08270-6) Genetic tumor syndromes in female cancer: insights into inherited cancer predisposition and clinical implications Annika Krückel1,2,3 · Julia Gocke1,2,3 · Manuel Hörner1,2,3 · Katharina Keller1,2,3 · Carolin Müller1,2,3 · Lena Brückner1,2,3 · Felix Heindl1,2,3 · Carolin C. Hack1,2,3 · Matthias W. Beckmann1,2,3 · Niklas Amann1,2,3 Received: 1 September 2025 / Accepted: 27 November 2025 © The Author(s) 2026 Abstract A relevant proportion of malignancies predominantly or exclusively affecting women, including breast and gynecologic cancers, is attributable to hereditary tumor syndromes, profoundly impacting cancer risk, prognosis, and therapeutic management. Today, the routine use of comprehensive germline panels has shifted the focus from solely pathogenic BRCA1/2 variants to include numerous pathogenic variants of other high-and moderate-risk genes. A broad spectrum of genetic alterations has been identified as causative for Hereditary Breast and Ovarian Cancer syndrome (HBOC), encompassing not only BRCA1 and BRCA2, but also PALB2, ATM, BARD1, CHEK2, BRIP1, RAD51C, and RAD51D. Beyond HBOC, numerous additional hereditary tumor syndromes are of significance in senologic and/or gynecologic oncology, including Li-Fraumeni syndrome, Lynch syndrome, DICER1 syndrome, Hereditary Diffuse Gastric Cancer, Neurofibromatosis type 1, PeutzJeghers syndrome, PTENhamartoma tumor syndrome, Tuberous Sclerosis, and pathogenic variants in NBN and SMARCA4 . Affected individuals are offered specialized surveillance to enable early detection or even prevention of cancer. In addition to regular clinical examinations and imaging, preventive strategies may include risk-reducing surgery. Pathogenic germline variants also influence therapeutic management of cancer patients. For specific indications, targeted therapies are available, for example PARP [poly (ADP-ribose) polymerase] inhibitors for pathogenic BRCA variant carriers across multiple tumor entities. Optimal management requires interdisciplinary coordination, encompassing genetic counseling, early detection, and risk-reducing strategies within specialized centers. This review provides a comprehensive overview of hereditary tumor syndromes predisposing to breast and gynecologic malignancies, with a focus on genetic basis, associated cancer risks, and implications for clinical management. By delineating these syndromes, it aims to assist clinicians in recognizing hereditary cancer predisposition and in guiding affected individuals within routine senologic and gynecologic practice. Keywords Tumor syndromes · Hereditary breast and ovarian cancer · Gynecologic malignancies · Endometrial cancer · Ovarian cancer · Cervical cancer · Breast cancer Abbreviations ACC BARD1 Adrenocortical carcinoma BRCA1-associated RING domain protein-1 * Annika Krückel [annika.krueckel@uk-erlangen.de](annika.krueckel@uk-erlangen.de) 1 Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Universitätsstraße 21/23, 91054 Erlangen, Germany 2 Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany 3 Bavarian Cancer Research Center (BZKF), Erlangen, Germany BRRS CDH1 CNS CPC CRCCS CTDGC EHTG ERN GENTURIS ESMO Bannayan–Riley–Ruvalcaba syndrome Cadherin-1 Central nervous system Choroid plexus carcinoma Colorectal cancer Cowden syndrome Computed tomography Diffuse-type gastric cancer European Hereditary Tumor Group European Reference Network for rare Genetic Tumor Risk Syndromes European Society for Medical Oncology GC-HBOC German Consortium for Familial Breast and Ovarian Cancer HBOC Hereditary Breast and Ovarian Cancer syndrome HDGC Hereditary Diffuse Gastric Cancer HNPCC Hereditary nonpolyposis colorectal cancer HPV Human papillomavirus IB

FAQs

Which female cancers are discussed as being influenced by hereditary tumor syndromes?

The text highlights breast and gynecologic malignancies, including ovarian and endometrial cancers, as being affected by hereditary tumor syndromes.

How has genetic testing changed the focus of hereditary cancer risk assessment?

Comprehensive germline panels have expanded attention from primarily pathogenic BRCA1/2 variants to many pathogenic variants in other high- and moderate-risk genes.

What clinical actions are offered to individuals with hereditary tumor syndromes?

Specialized surveillance is provided for early detection or prevention, alongside regular examinations and imaging; risk-reducing surgery may be used for prevention in appropriate cases.

Sep 22, 2026

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