Genetics: Beyond BRCA, Reem Saadeh-Haddad, MD
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Presented July 10, 2016 at the Ovarian Cancer National Conference in Washington, DC
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Genetics: Beyond BRCA, Reem Saadeh-Haddad, MD
- 1. Reem Saadeh, MD Clinical Geneticist
- 2. The Johns Hopkins Medicine Family Sibley Memorial Hospital colleagues and friends Ambry Genetic slides Myriad Genetic slides
- 4. Lifetime risk in the general population for sporadic cancer: ◦ Ovarian cancer: 1-2% ◦ Breast cancer: 8-12% for women <1% for men
- 7. Cause and age at death or current age Significant illnesses, physical findings that can be seen with other cancer syndromes Cancer screening and prophylactic or treatment surgical procedures that may decrease risk of another cancer Types of cancer-abdominal cancer, did that mean ovarian. 2nd cancers, primary vs metastasis
- 8. Frank (Myriad) model ◦ Relies on information regarding if and at what age first or second degree relatives with breast and/or ovarian cancer diagnosed ◦ Takes into consideration Ashkenazi Jewish heritage ◦ Does not take into consideration other cancers that can be associated with BRCA1/2 mutations ◦ www.brcacalculator.com BRCA-Pro ◦ Computer model that requires manual entry of each individual’s: History of cancer or risk reducing procedures ex. Oophorectomy Causes of death Age or age at death Ashkenazi Jewish heritage Genetic testing Gives other risk factors such as Gail risk if applicable ◦ http://www8utsouthwestern.edu/ut sw/cda/dept47829/files/65844.html
- 12. AJHG 1995;56:265-271 Science 2003: 643-646 JCO 2005 23 (8): 1656-63 NCI 2005 20 40 60 80 100 Breast cancer by age 50 Breast cancer by age 70 Ovarian cancer by age 70 2% Up to 50% 8% Up to 85% RiskofCancer(%) <1% Up to 50% General Population BRCA Mutation Lancet 1994;343:692-695 NEJM 1997;336:1401-1408 AJHG 2003;72:1117-1130
- 13. Lancet 1998;351:316-21 JCO 2004;22:2328-35 Lancet 1994;3343:692-5 Gynecol Oncol. 2005 Jan;96(1):222-6 0 20 40 60 Breast Cancer after 5 years Breast Cancer by age 70 Up to 3.5% Up to 27% Up to 11% Up to 65% RiskofCancer(%) General Population BRCA Mutation Ca Epi Biomarkers Prev. 1999;8(10):855-61 JNCI 1999;15:1310-6 JCO 1998;16:2417-25
- 14. JCO 2004;22: 735-42 NCI 2005 Breast Cancer by age 80 Prostate Cancer by age 80 General Population BRCA Mutation* 5 10 15 20 25 <1% 7% 15% 20% RiskofCancer(%) *Risks refer to BRCA2 mutation carriers. Risks for male BRCA1 mutation carriers are less characterized
- 15. JNCI 1999;15:1310-1316 JNCI 2002;94 1365-72 J Med Genet. 2005 Sep;42(9):711-9 Pancreatic cancer by age 80 General Population BRCA Mutation 5 15 20 25 <1% 2-4% RiskofCancer(%) 10 Melanoma by age 80 1% 2-4%
- 16. • Improved outcomes with proven medical interventions Surveillance Chemoprevention Prophylactic surgery • Treatment of manifestations in individuals with BRCA1 or BRCA2 related tumors is similar to that of sporadic forms of these cancers. JAMA 2000;283:617-24
- 17. ◦ Surveillance: Self breast exam q 1 mo (starting at age 18yr) Physician breast exam 4 times a year Mammograms once a year Breast MRI once a year ◦ Chemoprevention: Tamoxifen use has been associated with aTamoxifen use has been associated with a reduction of 53% in the risk of a second primaryreduction of 53% in the risk of a second primary breast cancer in contralateral cancersbreast cancer in contralateral cancers ◦ Prophylactic Surgery: Bilateral mastectomy reduces risk by >90%
- 18. Surveillance: ◦ Ovarian transvaginal u/s every 6-12 mo ◦ CA-125 –blood marker of ovarian ca every 6-12 mo Chemoprevention: ◦ Oral contraceptives,Oral contraceptives, when taken for 6 orwhen taken for 6 or more years, havemore years, have been associatedbeen associated with a reduction ofwith a reduction of up to 60% in the riskup to 60% in the risk of ovarian cancer.of ovarian cancer. ◦ Prophylactic Surgery Prophylactic oopherectomies reduces ovarian cancer risk by >95% Recommended after child bearing or 35-40 years. Removal of adjacent fallopian tubes is recommended as well and pathologic investigation of both at time of surgery Also has been shown to reduce the risk of breast cancer in mutation carriers.
- 19. Breast: ◦ Breast self exam—monthly ◦ Clinician breast exam—yearly ◦ Mammogram based on clinical findings Prostate ◦ Prostate specific antigen—yearly ◦ Digital rectal examination—yearly ◦ Begins same age as general population
- 22. Additional Genes: Majority risk here is for HNPCC: Hereditary Non polyposis CRC (HNPCC)
- 23. Due to mutations in: ◦ MLH1 ◦ MSH2 ◦ MSH6 ◦ PMS2 ◦ EPCAM Autosomal Dominant Inheritance
- 25. 0 20 40 60 80 100 CRC by age 50 CRC by age 70 EC by age 50 EC by age 70 General Population HNPCC RiskofCancer(%) 0.2% >25% 2% Up to 80% 0.2% 20% 1.5% Up to 71% Gastroenterology 1996;110:1020-7 Int J Cancer 1999;81:214-8 Gastroenterology 2004;127:17-25
- 26. 0 4 8 12 16 Ovarian Cancer Gastric Cancer General Population HNPCC RiskofCancer(%) Int J Cancer 1999;81:214-8 Stat Med 2003;22:1837-48 2% 12% <1% 13%
- 27. Additional cancers that have a lifetime risk of <5% ◦ Ureter/renal pelvis ◦ Biliary tract ◦ Small bowel ◦ Pancreas ◦ Brain ◦ Sebaceous adenoma Gastroenterology 1996;110:1020-7 Int J Cancer 1999;81:214-8
- 28. 0 20 40 60 Within 10 yrs Within 15 yrs General Population HNPCC RiskofCancer(%) Cancer 1977;40:1849 Dis Colon Rectum 1986;29:160 Cancer 1993;36:388-93 3.5% 30% 5% 50%
- 29. Improved outcomes with proven medical interventions Surveillance Surgery Gastroenterology 2000;118:829-34 Gastroenterology 2001;121:195-7 Dis Colon Rectum 2002;45:1588-94
- 30. Site Procedure Age to Begin Interval Colon Colonoscopy 20-25 1-2 years 40 Annually Endometrium & Ovaries Endometrial aspiration Transvaginal ultrasound CA-125 25-35 1-2 years JAMA 1997;277:915-19 Gastroenterology 2000;119:837-53 Gastroenterology 2001;121:198-213 Gastroenterology 2003;124:544-60
- 31. Colorectal cancer or more than one advanced adenoma ◦ Total Colectomy With ileorectal anastomosis (IRA) May be considered for patients unable/unwilling to undergo frequent colonoscopies ◦ Hemicolectomy With yearly colonoscopy Endometrial/Ovarian cancer ◦ Hysterectomy/salpingo-oophorectomy Option for HNPCC patients at time of any intra-abdominal surgery Option after childbearing is complete JAMA 1997;277:915-19 Gastroenterology 2001;121:198-213 Dis Colon Rectum 2003;46:1001-12
- 32. Additional Genes: Majority risk here is for HNPCC: Hereditary Non polyposis CRC (HNPCC)
- 34. It is important to remember that if a mutation is identified in the individual, then the following individuals are at a 50% risk of inheriting the same mutation: ◦ Each child of the individual ◦ Each sibling of the individual ◦ Each parent of the individual ◦ Extended relatives may be at risk ◦ All individuals should be made aware that a mutation has been identified in an individual in the family
- 35. Why get tested: ◦ Increased knowledge ◦ Health care decisions regarding ovarian cancer treatment and prevention ◦ Information for relatives ◦ Emotional benefits Why not get tested: ◦ Emotional implications ◦ Difficulties interpreting test results ◦ Test results may not change management guidelines.
- 36. Thank you! Reem Saadeh, MD Sibley Memorial Hospital 5255 Loughboro Road, NW Washington DC 20016 202-370-6546 rsaadeh1@jhmi.edu
Editor's Notes
- Average age of onset: 62yrs
- Ovarian cancer at any age A combination of breast and ovarian cancer especially if the breast cancer is age &lt;50, in a male or in multiple individuals. A combination of colon and ovarian, or ovarian and uterine either in the same individual or in multiple women in the family.
- Slide 4: A BRCA Mutation Increases Breast and Ovarian Cancer Risks Without intervention, the majority of women with inherited mutations in BRCA1 and BRCA2 will develop breast and/or ovarian cancer. The range of risks of breast and ovarian cancer associated with mutations in these genes has been characterized through numerous studies. The lower estimates of risk are derived from analysis of mutations in an unselected general population of individuals, whereas higher estimates of mutation-associated cancer risk are derived from families with a strong history of cancer. Generally, mutations in BRCA1 and BRCA2 are associated with a 45% to 87% risk of breast cancer by age 70. 1-3 Most importantly, hereditary breast cancer occurs at a far earlier age than the nonhereditary (sporadic) form. Women in the general population have only a 2% chance of developing breast cancer before age 50. However, a woman with a mutation in BRCA1 or BRCA2 has a 33% to 50% likelihood of developing breast cancer before reaching 50 years of age. 2,4 The risk of ovarian cancer due to inherited BRCA1 mutations is 28%7 to 44%1 by age 70, compared to the general population risk of &lt;1%. Mutations in BRCA2 confer a risk of ovarian cancer of 11%9 to 27%8 by age 70, which represents up to a 15-fold increase compared to the general population. References: 1. Ford D, et al. Breast Cancer Linkage Consortium: Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. 2. Struewing JP, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. NEJM 1997;336:1401-1408. 3. Antoniou A, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2mutations detected in case series unselected for family history: a combined analysis of 22 studies.AJHG 2003;72:1117-1130. 4.Easton DF, et al. Breast and ovarian cancer incidence in BRCA1-mutation carriers. AJHG1995;56:265-271. King MC, et al. Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2.Science Oct 24 2003:643-646. Narod SA, Offit K. Prevention and Management of Hereditary Breast Cancer. J Clin Oncol. 2005Mar 10;23(8):1656-63. 7. Whittemore AS, Gong G, Itnyre J. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer. Am J Hum Genet 1997;60:496-504. 8. Ford D, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. Am J Hum Genet 1998;62:676-689. 9. Antoniou A, et al. Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies. Am J Hum Genet. 2003 May; 72(5):1117-30. 10.DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0. Statistical Researchand Applications Branch, National Cancer Institute, 2005. http://srab.cancer.gov/devcan
- Slide 5 : A BRCA Mutation Increases the Risk of a Second Cancer Women who have developed breast cancer are at greatly increased risk of a second cancer if they carry a mutation in BRCA1 or BRCA2.2,4,5 The risk of a contralateral breast cancer is increased up to 64% by age 702, or 27.1% within five years of the initial diagnosis5 in women with BRCA1 mutations. Mutations in BRCA2 increase these risks to about 50% by age 70,3 or 23.5% within five years of the first breast cancer.5 References: 1.Frank TS, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with familyhistory and ovarian cancer risk. JCO 1998;16:2417-2425. 2.Ford D, et al. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343: 692-695. 3.The Breast Cancer Linkage Consortium. Cancer Risks in BRCA2 Mutation Carriers. JNCI1999;15:1310-1316. 4.Verhoog LC, et al. Survival and tumour characteristics of breast-cancer patients with germlinemutations of BRCA1. Lancet 1998;351:316-321. 5.Metcalfe K, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. JCO2004;22:2328-2335. 6. Metcalfe KA, et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers.Gynecol Oncol. 2005 Jan;96(1):222-6. 7.Chen Y, et al. Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev. 1999 Oct;8(10):855-61.
- Slide 7: Risks in Men with a BRCA Mutation To date, fewer men than women have undergone genetic testing for BRCA1 and BRCA2 mutations, in part because of misinformation about male cancer risks.1 However, men who carry BRCA1 or BRCA2 mutations have a significantly increased risk of cancer, with BRCA2 the more important gene for cancer susceptibility in men. In a study of BRCA2 families, the cumulative risk of all cancers in men was 32% by age 70, compared with 90% for women.2 For BRCA2 mutation carriers, the risk of male breast cancer by age 80 is approximately 7%.4 The risk of male breast cancer in BRCA1 families is less characterized, but is significantly higher than the general population risk. Mutations in BRCA2 also are associated with an increased risk of invasive prostate cancer (20% by age 80)2. In a recent case-control study of Ashkenazi Jewish men, BRCA2 mutation carriers had a nearly 5-fold increased risk of prostate cancer.3 A modestly increased risk of prostate cancer was reported in men under age 65 with BRCA1 mutations.4 References: 1.Liede A, et al. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: A reviewof the literature. JCO 2004;22:735-42. 2.The Breast Cancer Linkage Consortium: Cancer Risks in BRCA2 Mutation Carriers. Journal of theNational Cancer Institute 1999;15:1310-1316. 3.Kirchhoff T, et al. BRCA mutations and risk of prostate cancer in Ashkenazi Jews. Clinical CancerResearch 2004;10:2918-2. 4.Thompson D, Easton D; Breast Cancer Linkage Consortium. Variation in cancer risks, by mutationposition, in BRCA2 mutation carriers. Am J Hum Genet. 2001 Feb;68(2):410-9. Epub 2001 Jan 19. 5.Thompson D, et al. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002 Sep 18;94 (18):1358-65. 6.DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0. Statistical Researchand Applications Branch, National Cancer Institute, 2005. http://srab.cancer.gov/devcan.
- Slide 8: Risks of Other Cancers Both men and women with mutations in BRCA1 or BRCA2 have an elevated risk of pancreatic cancer compared to the general population, although the lifetime risk of this rare cancer is still low (2%-4%) even for individuals with these mutations. 1,2 A two-fold increase in relative risk of colorectal cancer has been described for BRCA1 mutation carriers when compared to the general population.2,3 However, additional studies have not observed this increased risk, so a true association remains unclear.4 No increased risk of colorectal cancer has been observed in the BRCA2 population.1,4,5 An increased risk of melanoma has been described in BRCA2 mutation carriers with a 2.5 increase in relative risk compared to the general population.1 An increased risk of melanoma in BRCA1 mutation carriers has not been observed. There are currently no increased screening recommendations for pancreatic cancer, colon cancer, and melanoma, in mutation positive individuals. For male associated cancers the NCCN has specific guidelines outlined on Slide 17. References: 1.The Breast Cancer Linkage Consortium: Cancer Risks in BRCA2 Mutation Carriers. JNCI1999;15:1310-1316. 2.Thompson D, et al. Cancer Incidence in BRCA1 mutation carriers. JNCI 2002;94:1358-65. 3.Brose MS, et al. Cancer Risk Estimates for BRCA1 Mutation Carriers Identified in a RiskEvaluation Program. JNCI. 2002;94 1365-72. 4.Lin KM, et al: Colorectal cancer in hereditary breast cancer kindreds. Diseases of the Colon andRectum 1999;42:1041-1045. 5.van Asperen CJ, et al. Cancer risks in BRCA2 families: estimates for sites other than breast andovary. J Med Genet. 2005 Sep;42(9):711-9.
- Slide 9: Managing Hereditary Cancer Risk A discussion of the likelihood of carrying a mutation and the associated risks of cancer should occur in the context of available medical interventions to address those risks. The benefits and limitations of increased surveillance, chemoprevention, and prophylactic surgery should each be considered for women with hereditary risk. Over the past few years, numerous published studies have documented the efficacy of various medical management options in reducing cancer risk among carriers of a BRCA1 or BRCA2 mutation. References: 1.Frank TS, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family historyand ovarian cancer risk. JCO 1998;16:2417-2425. 2.The Breast Cancer Linkage Consortium: Cancer Risks in BRCA2 Mutation Carriers. JNCI1999;15:1310-1316. 3.Verhoog LC, et al. Survival and tumour characteristics of breast-cancer patients with germlinemutations of BRCA1. Lancet 1998;351:316-321. 4.Verhoog LC, et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2.JCO 1999;17:3396-3402. 5.Schrag D, et al. Life expectancy gains from cancer prevention strategies for women with breast cancerand BRCA1 or BRCA2 mutations. JAMA 2000;283:617-624. 6.Narod SA, Offit K. Prevention and Management of Hereditary Breast Cancer. J Clin Oncol. 2005Mar 10; 23(8):1656-63.
- Ca 125 high false positive rate
- Age 50 years for general population, high risk is 45 years old
- Slide 9: HNPCC Increases Colorectal and Endometrial Cancer Risks The risk of colorectal cancer in the general population is about 0.2% by the age of 50 and 2% by the age of 70. The risk of endometrial cancer in the general population is about 0.2% by the age of 50 and less than 2% by the age of 70.1 Without medical intervention, most people with inherited mutations in the mismatch repair genes will develop colorectal cancer. The risk of colorectal cancer in mutation carriers is at least 25% by age 50 and about 80% by age 70.2,3 It must be emphasized that although adenomatous polyps may form at a relatively early age in patients with HNPCC, a profusion of polyps is not a feature of HNPCC. Early onset of colorectal cancer is one hallmark of HNPCC but may not always be present in these families. For example, while the average age of diagnosis of colorectal cancer is 43-44 years in MLH1 and MSH2 mutation carriers, families with MSH6 mutations have an average age of colorectal cancer onset of approximately 54-55 years.4 Additionally, women who inherit HNPCC-associated germline mutations also have a greatly elevated risk of endometrial cancer. The risk of endometrial cancer in MLH1 and MSH2 carriers is 20% by age 50 and up to 60% by age 70.2,3 Recent literature on MSH6 suggests that carriers of mutations in MSH6 may have as high as a 71% chance to develop endometrial cancer.3 As with colorectal cancer, endometrial cancer in patients with MLH1 and MSH2 mutations occurs at a younger age, often before age 50. Again the age of onset of endometrial cancer in those with MSH6 mutations is slightly later with a mean age of 54 years.4 Some studies have reported that if a woman carries an MLH1, MSH2, or MSH6 mutation, her risk of endometrial cancer may be even higher than her risk of colorectal cancer.3 Early onset of endometrial cancer should therefore raise suspicion for HNPCC, especially in women with a family history of colorectal cancer or endometrial cancer. References: 1Fay MP, Pfeiffer R, Cronin KA, et al. Age-conditional probabilities of developing cancer. Statistics in Medicine 2003;22:1837-48. 2Vasen HFA, Wijnen JT, Menko FH, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 1996;110:1020-7. 3Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. International Journal of Cancer 1999;81:214-8. 4Hendriks YM, Wagner A, Morreau H, et al. Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: Impact on counseling and surveillance. Gastroenterology 2004;127:17-25.
- Slide 10: HNPCC Increases Ovarian and Gastric Cancer Risks HNPCC is associated with an increased risk of gastric and ovarian cancers, estimated to be slightly higher than 10% for each by the age of 70.1 This is compared to the general population risk of 2% and less than 1%, respectively.2 References: 1Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. International Journal of Cancer 1999;81:214-8. 2Fay MP, Pfeiffer R, Cronin KA, et al. Age-conditional probabilities of developing cancer. Statistics in Medicine 2003;22:1837-48.
- Slide 11: HNPCC Increases the Risks of Other Cancers HNPCC also increases the risks of various other cancers, including those of the ureter/renal pelvis, biliary tract, small bowel, pancreas and brain. Each of these cancer risks is below 5% during a person’s lifetime.1,2 Sebaceous skin tumors also occur in some patients and are a characteristic feature of a rare variant of HNPCC called Muir-Torre syndrome.2,3 When HNPCC occurs along with CNS tumors (usually, glioblastoma), this condition is called Turcot syndrome.4 References: 1Aarnio M, Sankila R, Pukkala E, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. International Journal of Cancer 1999;81:214-8. 2Vasen HFA, Wijnen JT, Menko FH, et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 1996;110:1020-7. 3Kruse R, Rutten A, Lamberti C, et al. Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria. American Journal of Human Genetics 1998;63:63-70. 4Hamilton SR, Liu B, Parsons RE, et al. The molecular basis of Turcot&apos;s syndrome. New England Journal of Medicine 1995;332:839-47.
- Slide 12: HNPCC Increases Risk of Second Cancer Colon cancer patients with HNPCC are at high risk of developing a second primary cancer, especially of the colon or endometrium. For these individuals, the risk of a second HNPCC-associated cancer is estimated to be 30% within 10 years of the first cancer diagnosis and 50% within 15 years of the first cancer diagnosis. These risks include the risk of a second colorectal cancer.1,2 Therefore, surgical treatment of patients with HNPCC-associated colorectal cancer must be based not only on treating the first primary cancer but also the prevention of a second colorectal cancer. In addition, women with HNPCC who develop endometrial cancer are at greatly increased risk of subsequent colorectal cancer. Knowledge of these significant risks for second cancers can be useful in planning appropriate interventions for individuals with HNPCC. References: 1Lynch HT, Harris RE, Lynch PM, et al. Role of heredity in multiple primary cancer. Cancer 1977;40:1849-54. 2Mecklin JP, Jarvinen HJ. Clinical features of colorectal carcinoma in cancer family syndrome. Diseases of the Colon and Rectum 1986;29:160-4. 3Cali RL, Pitsch RM, Thorson AG, et al. Cumulative incidence of metachronous colorectal cancer. Diseases of the Colon and Rectum 1993;36:388-93.
- Slide 13: Managing Hereditary Cancer Risk in HNPCC Over the past few years, numerous published studies have documented the efficacy of various medical management options in reducing cancer risk among individuals with HNPCC.1-3 References: 1Jarvinen HJ, Aarnio M, Mustonen H, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118:829-34. 2De Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, et al. Surveillance for hereditary nonpolyposis colorectal cancer: a long term study on 114 families. Diseases of the Colon and Rectum 2002;45:1588-94. 3American Gastroenterological Association Medical Position Statement: Hereditary colorectal cancer and genetic testing. Gastroenterology 2001;121:195-7.
- Slide 14: HNPCC Surveillance Guidelines To detect colorectal cancer or polyps in individuals at risk of HNPCC, the American Gastroenterological Association recommends colonoscopic surveillance every one to two years, beginning between the ages of 20 to 25, with annual screening after age 40.1-3 Although surveillance for endometrial and ovarian cancer is less well established, recommended measures include annual transvaginal ultrasound and/or endometrial aspiration, and CA-125 testing beginning between ages 25 and 35. However, the efficacy of endometrial and ovarian cancer screening measures has not yet been proven.1,4 Surveillance for other HNPCC–related cancers, such as gastric cancer, may be recommended based on their presence in the family history.2 References: 1Giardiello FM, Brensinger JD, Petersen GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 2001;121:198-213. 2Burt R. Colon cancer screening. Gastroenterology 2000;119:837-53. 3Winawer S, Fletcher R, Rex D, et al. Colorectal cancer screening and surveillance: clinical guidelines and rationale – update based on new evidence. Gastroenterology 2003;124:544-60. 4Burke W, Petersen G, Lynch P, et al. Recommendations for follow-up care of individuals with inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Journal of the American Medical Association 1997;277:915-19.
- Slide 16: HNPCC Surgical Guidelines Approximately half of HNPCC patients with CRC will develop a second primary CRC within 15 years of their initial diagnosis. For this reason, the American Society of Colon and Rectal Surgeons recommends a total colectomy with ileorectal anastomosis OR a hemicolectomy for CRC patients with HNPCC. These surgeries are also options for HNPCC patients who develop advanced adenomas, as well as for those who are unwilling or unable to undergo regular colonoscopy.1-3 Women who are mutation-positive may consider prophylactic surgery to remove the uterus and ovaries to substantially reduce the risk of endometrial and ovarian cancer. This procedure may take place at the time of a CRC diagnosis or once childbearing is completed.1,2 References: 1Church J, Simmang C. Practice parameters for the treatment of patients with dominantly inherited colorectal cancer (familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer). Diseases of the Colon & Rectum 2003;46:1001-12. 2Giardiello FM, Brensinger JD, Petersen GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology 2001;121:198-213. 3Burke W, Petersen G, Lynch P, et al. Recommendations for follow-up care of individuals with inherited predisposition to cancer. I. Hereditary nonpolyposis colon cancer. Journal of the American Medical Association 1997;277:915-19.