Recommendations for Follow-up Care of Individuals with Inherited Susceptibility to Cancer

1. HNPCC-Associated Mutations
   
2. BRCA1 and BRCA2 Mutations

Summary

The task force has developed provisional recommendations for carriers of BRCA1, BRCA2, and HNPCC-associated mutations as outlined below, based on a review of studies evaluating cancer risk, cancer surveillance and risk reduction in individuals genetically susceptible to breast and ovarian cancer. The quality of evidence for each measure was assessed using criteria of the U.S. Preventive Services Task Force, where I = highest quality, e.g., evidence from randomized trials and III = lowest quality, e.g., case reports and expert opinion. Review of the available evidence indicates that the efficacy of cancer surveillance in genetically susceptible individuals is unknown. Individuals thus should be counseled about the lack of proven benefit of surveillance measures and about potential risks -- e.g., the potential of increased breast cancer risk with early exposure to mammography. Prophylactic surgery is another option for genetically susceptible individuals, but evidence of benefit is also lacking for these procedures. Estimates of cancer risk associated with BRCA1, BRCA2 and HNPCC-associated mutations are an additional source of uncertainty. Current risk estimates are derived from families collected for research purposes, who have met stringent criteria for autosomal dominant inheritance of cancer predisposition and are characterized by early onset of cancer and/or multiple tumors -- i.e., families that have been selected for high penetrance. Predictions of risk and follow-up recommendations are likely to change as new evidence emerge.

Options for Surveillance -- Carriers of HNPCC-Associated Mutations

Intervention	Provisional Recommendation	Quality of Evidence	Cautionary Issues
Colonoscopy	Begin at age 20-25 Repeat every 1-3 years	II-3-Evidence from multiple time series with and without the intervention	Insufficient data to determine optimal screening interval
Transvaginal pelvic ultrasound or endometrial aspirate	Annually, beginning at age 25-35	III-Expert opinion only	Benefit not proven Limited sensitivity

Options for Prophylactic Surgery -- Carriers of HNPCC-Associated Mutations

Surgery	Provisional Recommendation	Quality of Evidence	Cautionary Issues
Transabdominal hysterectomy and bilateral oophorectomy	Insufficient evidence to recommend for or against the intervention	III-Expert opinion only	Efficacy uncertain. Risk not fully eliminated
Colectomy	Insufficient evidence to recommend for or against the intervention	III-Expert opinion only	Efficacy uncertain. Risk not fully eliminated

Options for Prophylactic Surgery -- Carriers of BRCA1 and BRCA2 Mutations

Hormone Replacement Therapy and Hormonal Contraception

There are insufficient data to make a recommendation concerning use or avoidance of estrogen therapy by BRCA1 and BRCA2 mutation carriers. In weighing the question, individuals should be counseled that treatment with estrogen, with or without progestin, may increase breast cancer risk. However, use of oral contraceptives may reduce ovarian cancer risk. Hormonal therapy may be beneficial in treating menopausal symptoms, and in prevention of cardiac disease and osteoporosis; these factors should also be taken into account in making individual decisions about the use of estrogen.

Lifestyle Modification

The task force endorses counseling regarding the possible health benefit of low-fat, high fiber diets, adequate intake of vegetables and fruit, regular exercise, and avoidance of exposure to known carcinogens. These measures are an unproven means to reduce cancer risk but have a broad range of other health benefits, and do not pose the risks of pharmacologic or procedural interventions. In addition, some individuals with an inherited predisposition to cancer may welcome the opportunity to take active steps to promote improved health. At the same time, sufficient explanation should be provided concerning the uncertainty of benefits in cancer risk reduction to permit latitude for individual choice.