Hereditary Breast and Ovarian Cancer How big a problem? How far have we gotten?

1. Hereditary Breast and Ovarian CancerHow big a problem?How far have we gotten? Kevin S.Hughes, MD, FACS Co-Director, Avon Comprehensive Breast Evaluation Center Massachusetts General Hospital Surgeon The Newton-Wellesley Hospital Breast Center

2. Identify patients before they develop cancer • Prevent cancer • Find it at an earlier stage • If cancer develops, choices easier • Help relatives

3. Our Goal Find every mutation carrier for every hereditary syndrome known to man before disease occurs

4. Adult hereditary syndromes: 188 • Scheuner (Am J Med Gen, 2004)

5. Problems to solve • Most high risk women not identified • If identified, Risk Clinics could not manage the volume

6. BRCA1/2 Mutation carriers in the US ~1,000,000 carriers

7. BRCA1/2 Mutation carriers in the US ~1,000,000 carriers

8. BRCA1/2 Mutation carriers in the US ~1,000,000 carriers

9. BRCA1/2 Mutation carriers in the USFemales 20 and above Close to 350,000 carriers 20 and older

10. BRCA tests: Myriad Genetics ~500,000 Ordered by ~40,000 providers Courtesy of Myriad Genetics

11. 15 years of genetic testing • Assume 10% positive • 50,000 BRCA1/2 carriers found • Assume most tested patients had cancer • 95 to 99% of unaffected carriers not tested Likely the best of any adult hereditary syndrome

12. Estimated US Cancers 2010 Invasive breast   207,090 In situ breast 54,010 Ovary 21,880 Total 282,980 5% Hereditary = 14,149 Few were identified before they developed cancer Many never identified

13. Find all mutation carriers Family history & selective testing Population based genetic testing

14. Find all mutation carriers Family history & selective testing Population based genetic testing Adult syndromes Newborn screening

15. CANCER SPORADIC HEREDITARY CANCER Hereditary vs Sporadic Cancer Knudson’s 2 hit hypothesis

16. Family history Multiple relatives affected Young age at diagnosis Multiple primary cancers Unusual Cancer Male breast cancer

17. NCCN Practice Guidelines (2005) • 2. Personal history of breast cancer plus one or more of the following: • a) Diagnosed under 40 years, with or without family history • b) Diagnosed under 50 years, or bilateral, with at least one close blood relative with breast cancer diagnosed under 50 years or at least one close blood relative with ovarian cancer • c) Diagnosed at any age, with at least two close blood relatives with ovarian cancer at any age • d) Diagnosed at any age with breast cancer with at least two close* blood relatives with breast cancer, especially if at least one is diagnosed before age 50 years or has bilateral • disease • e) Close male blood relative has breast cancer • f) Personal history of ovarian cancer • g) Is of ethnic descent associated with deleterious mutations (e.g., Ashkenazi Jewish) • 1. Member of a family with a known BRCA1/BRCA2 mutation • 2. Personal history of breast cancer plus one or more of the following: • a) Diagnosed 40 years, with or without family history • b) Diagnosed 50 years, or bilateral, with at least one close blood relative with breast cancer diagnosed 50 years or at least one close blood relative with ovarian cancer • c) Diagnosed at any age, with at least two close blood relatives with ovarian cancer at any age • d) Diagnosed at any age with breast cancer with at least two close* blood relatives with breast cancer, especially if at least one is diagnosed before age 50 years or has bilateral • disease • e) Close male blood relative has breast cancer • f) Personal history of ovarian cancer • g) Is of ethnic descent associated with deleterious mutations (e.g., Ashkenazi Jewish) • 3. Personal history of ovarian cancer plus one or more of the following: • a) At least one close* blood relative with ovarian cancer • b) At least one close* female blood relative with breast cancer • at age 50 years or bilateral breast cancer • c) At least two close* blood relatives with breast cancer • d) At least one close* male blood relative with breast cancer • e) Is of Ashkenazi Jewish descent • 4. Personal history of male breast cancer plus one or more of the following: • a) At least one close male blood relative with breast cancer • b) At least one close female blood relative with breast or ovarian cancer • c) Ashkenazi Jewish descent • 5. Family history only: close family member (on the same side of the family) meeting any of the above criteria

18. Risk Models

19. BRCAPRO

20. Dependant on paper form plus memory

21. Currently: Paper + memory Patient completes paper form Reviews data using memory of guidelines Orders Genetic Testing

22. EHR: Paper + extra work + memory Patient completes paper form Staff enters data into the EHR Reviews data using memory of guidelines Orders Genetic Testing

23. Memory-Based Medicine  “Current medical practice relies heavily on the unaided mind to recall a great amount of detailed knowledge”  Crane, Raymond, The Permanente Journal 7:62, 2003

24. Clinical Decision Support (CDS) Apply Algorithms/Guidelines to patient data Identify best course of action Results displayed as intuitive Visualizations BRCAPRO Mutation Risk 25% Suggest Genetic Testing Facilitates best action as part of workflow

25. HughesRiskApps modules follow a simple workflow Patient data entry Clinical Decision Support (CDS) Printout with suggested actions

26. HughesRiskApps.com Patient enters data into Tablet PC or iPad Patient educational materials Clinical Decision Support Reviews Report & Pedigree Reviews suggested management Orders Genetic Testing

27. Newton Wellesley HospitalSince 4/2007 • 49758 unique patients • 2255 (4.5%) mutation risk 10% or greater

28. Women at elevated risk and their PCP are sent a letter

30. DEMO

31. Uptake is poor

32. Monitor uptake on counseling

33. Simplify Contact

34. Simplify contact and record outcome

35. If patient declines, record reason

36. Conclusions Begin the process of finding every mutation carrier for every hereditary syndrome known to man before disease occurs HughesRiskApps.com

38. If mutation is found-Find all positive family members Mutation Found Selective Testing Cascade Testing of family members

39. Breast Imager receives a printout of risk factors and scores

40. HughesRiskApps modules follow a simple workflow Patient data entry Clinical Decision Support (CDS) Printout with suggested actions Clinician editing/enhancing Clinical Decision Support (CDS) Generate orders and documents

41. Software • CancerGene (Euhus) • HughesRiskApps.com

42. Risk Models

43. US population Census, 2000

44. 14 years of genetic testing ~50,000 BRCA1/2 carriers found Likely the best of any adult hereditary syndrome

45. National Health Interview Surveys 2000 & 200535,116 unaffected women 0.96% high risk for hereditary breast/ovarian cancer • 54% aware of genetic testing • 10.4% had discussed genetic testing with Clinician 1.4% had undergone genetic testing Levy et al. Guidelines for Genetic Risk Assessment of Hereditary Breast and Ovarian Cancer: Early Disagreements and Low Utilization. J Gen Int Med

46. BRCA1/2 Mutation carriers in the US ~1,000,000 carriers

47. Our Goal Find every mutation carrier for every hereditary syndrome known to man before disease occurs HughesRiskApps.com

48. National Health Interview Surveys 2000 & 200535,116 unaffected women 0.96% high risk for hereditary breast/ovarian cancer • 54% aware of genetic testing • 10.4% had discussed genetic testing with Clinician 1.4% had undergone genetic testing Levy et al. Guidelines for Genetic Risk Assessment of Hereditary Breast and Ovarian Cancer: Early Disagreements and Low Utilization. J Gen Int Med

49. Primary Care Provider • Know 188 syndromes • Know Models to quantitate risk • Know guidelines for who to refer

50. Dependant on paper form plus memory