title: Breast cancer risk and clinical implications for germline PTEN mutation carriers.
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.
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore, 169610, Singapore.|Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, 169610, Singapore.|Cleveland Clinic, Genomic Medicine Institute, 9500 Euclid Avenue, NE-50, Cleveland, OH, 44195, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
authors.affiliation: Cleveland Clinic, Genomic Medicine Institute, 9500 Euclid Avenue, NE-50, Cleveland, OH, 44195, USA.|Cleveland Clinic, Lerner Research Institute, Cleveland, OH, 44195, USA.|Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, 44195, USA.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Sesock
authors.affiliation: Cleveland Clinic, Genomic Medicine Institute, 9500 Euclid Avenue, NE-50, Cleveland, OH, 44195, USA. engc@ccf.org.|Cleveland Clinic, Lerner Research Institute, Cleveland, OH, 44195, USA. engc@ccf.org.|Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, 44195, USA. engc@ccf.org.|Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. engc@ccf.org.|Germline High Risk Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA. engc@ccf.org.
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019683:Penetrance; D010641:Phenotype; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Breast cancer; Cowden syndrome; PTEN; PTEN hamartoma tumor syndrome