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Breast cancer risk and clinical implications for germline PTEN mutation carriers

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Abstract

PTEN Hamartoma Tumor syndrome (PHTS) encompasses a clinical spectrum of heritable disorders including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome, and Proteus and Proteus-like syndrome that are associated with germline mutations in the PTEN tumor suppressor gene. Breast cancer risk estimates (67–85 %) for women with germline PTEN mutations are similar to those quoted for patients with germline mutations in the BRCA1/2 genes. With PTEN on several germline gene testing panels, finding PTEN mutations and variants have increased exponentially. PHTS can be differentiated from other hereditary cancer syndromes including Hereditary Breast Ovarian Cancer syndrome, Lynch syndrome, and hamartomatous polyposis syndromes based on personal as well as family history. However, many of the benign features of CS are common in the general population, making the diagnosis of CS challenging. Breast cancer patients with an identified germline PTEN mutation are at increased risk of endometrial, thyroid, renal, and colorectal cancers as well as a second breast cancer. Increased screening for the various component cancers as well as predictive testing in first-degree relatives is recommended. Prophylactic mastectomy may be considered especially if breast tissue is dense or if repeated breast biopsies have been necessary. Management of women with breast cancer suspected of CS who test negative for germline PTEN mutations should be managed as per a mutation carrier if she meets CS diagnostic criteria, and should be offered enrollment in research to identify other predisposition genes.

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Acknowledgments

We are grateful to all our research participants and their families, and all their multidisciplinary caregivers. JN is funded by the National Medical Research Council Singapore (Transition Award). CE is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine at the Cleveland Clinic, and an ACS Clinical Research Professor.

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Authors and Affiliations

  1. Division of Medical Oncology, National Cancer Centre, Singapore, 169610, Singapore

    Joanne Ngeow

  2. Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, 169610, Singapore

    Joanne Ngeow

  3. Cleveland Clinic, Genomic Medicine Institute, 9500 Euclid Avenue, NE-50, Cleveland, OH, 44195, USA

    Joanne Ngeow, Kaitlin Sesock & Charis Eng

  4. Cleveland Clinic, Lerner Research Institute, Cleveland, OH, 44195, USA

    Kaitlin Sesock & Charis Eng

  5. Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, 44195, USA

    Kaitlin Sesock & Charis Eng

  6. Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA

    Charis Eng

  7. Germline High Risk Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA

    Charis Eng

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  1. Joanne Ngeow
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  2. Kaitlin Sesock
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Correspondence to Charis Eng.

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Ngeow, J., Sesock, K. & Eng, C. Breast cancer risk and clinical implications for germline PTEN mutation carriers. Breast Cancer Res Treat 165, 1–8 (2017). https://doi.org/10.1007/s10549-015-3665-z

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