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ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes

José G. Guillem, William C. Wood, Jeffrey F. Moley, Andrew Berchuck, Beth Y. Karlan, David G. Mutch, Robert F. Gagel, Jeffrey Weitzel, Monica Morrow, Barbara L. Weber, Francis Giardiello, Miguel A. Rodriguez-Bigas, James Church, Stephen Gruber, Kenneth Offit

From the Departments of Surgery and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Surgery, Emory University School of Medicine, Atlanta, GA; Department of Surgery, Washington University School of Medicine, St Louis, MO; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC; Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO; Department of Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Clinical Cancer Genetics, City of Hope National Medical Center, Duarte, CA; Department of Surgery, Fox Chase Cancer Center; Departments of Medicine and Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Colorectal Surgery, The Cleveland Clinic Foundation, Cleveland, OH; and the Department of Medicine, The University of Michigan Medical Center, Ann Arbor, MI

Address reprint requests to José G. Guillem, MD, MPH, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C-1077, New York, NY 10021; e-mail: guillemj{at}mskcc.org

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' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been published jointly by invitation and consent in both the Journal of Clinical Oncology and the Annals of Surgical Oncology. © 2006 Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the Society of Surgical Oncology.

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