NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Lynch HT, Watson P, Conway TA, Lynch JF. Clinical/genetic features in hereditary breast cancer. Breast Cancer Res Treat 1990;15:63–71.
Pharoah PD, Day NE, Duffy S. Family history and the risk of breast cancer: a systematic review and meta-analysis. Int J Cancer 1997;71:800–809.
Berliner JL, Fay AM. Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors. J Genet Couns 2007;16:241–260.
Trepanier A, Ahrens M, McKinnon W. Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns 2004;13:83–114.
Pharoah PD, Antoniou A, Bobrow M. Polygenic susceptibility to breast cancer and implications for prevention. Nat Genet 2002;31:33–36.
Eng C. PTEN hamartoma tumor syndrome (PTHS). In: Pagon RA, Adam MP, Ardinger HH, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2014. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1488/. Accessed August 5, 2014.
Pilarski R, Stephens JA, Noss R. Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet 2011;48:505–512.
Varga EA, Pastore M, Prior T. The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders, developmental delay, and macrocephaly. Genet Med 2009;11:111–117.
Lloyd KM 2nd, Dennis M. Cowden’s disease. A possible new symptom complex with multiple system involvement. Ann Intern Med 1963;58:136–142.
Nelen MR, Kremer H, Konings IB. Novel PTEN mutations in patients with Cowden disease: absence of clear genotype-phenotype correlations. Eur J Hum Genet 1999;7:267–273.
Pilarski R, Eng C. Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet 2004;41:323–326.
Starink TM, van der Veen JP, Arwert F. The Cowden syndrome: a clinical and genetic study in 21 patients. Clin Genet 1986;29:222–233.
Riegert-Johnson DL, Gleeson FC, Roberts M. Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients. Hered Cancer Clin Pract 2010;8:6.
Bubien V, Bonnet F, Brouste V. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J Med Genet 2013;50:255–263.
Black D, Bogomolniy F, Robson ME. Evaluation of germline PTEN mutations in endometrial cancer patients. Gynecol Oncol 2005;96:21–24.
Schaffer JV, Kamino H, Witkiewicz A. Mucocutaneous neuromas: an underrecognized manifestation of PTEN hamartoma-tumor syndrome. Arch Dermatol 2006;142:625–632.
Jazaeri AA, Lu K, Schmandt R. Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma. Mol Carcinog 2003;36:53–59.
Heald B, Mester J, Rybicki L. Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers. Gastroenterology 2010;139:1927–1933.
Al-Thihli K, Palma L, Marcus V. A case of Cowden’s syndrome presenting with gastric carcinomas and gastrointestinal polyposis. Nat Clin Pract Gastroenterol Hepatol 2009;6:184–189.
Zhou XP, Waite KA, Pilarski R. Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J Hum Genet 2003;73:404–411.
Andres RH, Guzman R, Weis J. Lhermitte-Duclos disease with atypical vascularization—case report and review of the literature. Clin Neuropathol 2009;28:83–90.
Butler MG, Dasouki MJ, Zhou XP. Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. J Med Genet 2005;42:318–321.
Herman GE, Butter E, Enrile B. Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly. Am J Med Genet A 2007;143:589–593.
Marsh DJ, Coulon V, Lunetta KL. Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet 1998;7:507–515.
Tan MH, Mester J, Peterson C. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet 2011;88:42–56.
Pilarski R, Burt R, Kohlman W. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst 2013;105:1607–1616.
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. SEER Stat Fact Sheets: Thyroid Cancer. Available at: http://seer.cancer.gov/statfacts/html/thyro.html. Accessed August 5, 2014.