title: ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes.
abstract: Although the etiology of solid cancers is multifactorial, with environmental and genetic factors playing a variable role, a significant portion of the burden of cancer is accounted for by a heritable component. Increasingly, the heritable component of cancer predispositions has been linked to mutations in specific genes, and clinical interventions have been formulated for mutation carriers within affected families. The primary interventions for mutations carriers for highly penetrant syndromes such as multiple endocrine neoplasias, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and hereditary breast and ovarian cancer syndromes are primarily surgical. For that reason, the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) have undertaken an educational effort within the oncology community. A joint ASCO/SSO Task Force was charged with presenting an educational symposium on the surgical management of hereditary cancer syndromes at the annual ASCO and SSO meetings, resulting in an educational position article on this topic. Both the content of the symposium and the article were developed as a consensus statement by the Task Force, with the intent of summarizing the current standard of care. This article is divided into four sections addressing breast, colorectal, ovarian and endometrial cancers, and multiple endocrine neoplasia. For each, a brief introduction on the genetics and natural history of the disease is provided, followed by a detailed description of modern surgical approaches, including a description of the clinical and genetic indications and timing of prophylactic surgery, and the efficacy of prophylactic surgery when known. Although a number of recent reviews have addressed the role of genetic testing for cancer susceptibility, including the richly illustrated Cancer Genetics and Cancer Predisposition Testing curriculum by the ASCO Cancer Genetics Working Group (available through http://www.asco.org), this article focuses on the issues surrounding the why, how, and when of surgical prophylaxis for inherited forms of cancer. This is a complex process, which requires a clear understanding of the natural history of the disease and variance of penetrance, a realistic appreciation of the potential benefit and risk of a risk-reducing procedure in a potentially otherwise healthy individual, the long-term sequelae of such surgical intervention, as well as the individual patient and family's perception of surgical risk and anticipated benefit.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. guillemj@mskcc.org
authors.forename: José G
authors.initials: JG
authors.lastname: Guillem
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Moley
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Karlan
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Robert F
authors.initials: RF
authors.lastname: Gagel
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weitzel
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: Francis
authors.initials: F
authors.lastname: Giardiello
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rodriguez-Bigas
authors.forename: James
authors.initials: J
authors.lastname: Church
authors.forename: Stephen
authors.initials: S
authors.lastname: Gruber
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000379:methods* / Q000639:trends; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000601:surgery*; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000601:surgery*; D012306:Risk; D018570:Risk Assessment; D012955:Societies, Medical; D016896:Treatment Outcome; D014481:United States