1. Kevin S.Hughes, MD, FACS Co-Director, Avon Comprehensive Breast Evaluation Center Massachusetts General Hospital Surgeon The Newton-Wellesley Hospital Breast Center Identification and Management of Women at High Risk for Hereditary Breast and Ovarian Cancer

2. DISCLOSURES HughesRiskApps.Net Open Access Solution http://www.HughesRiskApps.com Speaker’s Bureau Myriad Genetics kshughes@partners.org http://www.HughesRiskApps.com kshughes@partners.org

3. Cancer Risk Breast 50-87% 50-87% Ovary 40-60% 10-20% Breast 6% FemaleMaleFemaleMale BRCA1BRCA2

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

5. Family history Multiple relatives affected Young age at diagnosis Multiple primary cancers Male breast cancer

6. Options for high risk

8. Prophylactic Oophorectomy Screening Chemoprevention Options for high risk

9. HRT Use:Never Post-RRSO RRSO:NoYes Mean age at RRSO--45.0 (20.5-79.0)40.8 (29.4-63.4) Mean age at start of follow up34.4 (18.1-90.4)-- Mean follow-up to BC4.8 (0.5-17.6)2.7 (0.5-6.0)4.9 (0.8-20.2) Mean age at BC40.9 (22.2-71.9)46.3 (33.3-63.3)46.5 (36.1-63.1) Mean follow-up to censoring (Yrs)5.1 (0.5-27.8)3.6 (0.5-18.8)5.4 (0.6-27.4) Total Sample (N)867177144 BC Diagnosed During FU194 (22%)22 (12%)20 (14%) HR (95% CI)[1]0.56 (0.34-0.93)0.43 (0.26-0.72) BRCA1 (N)520115105 BC Diagnosed During FU118 (23%)16 (14%)17 (16%) HR (95% CI)[1]0.58 (0.32-1.05)0.49 (0.28-0.86) BRCA2 (N)3476239 BC Diagnosed During FU76 (22%)6 (10%)3 (8%) HR (95% CI)[1]0.46 (0.18-1.13)0.22 (0.05-1.00) Adjusted for age at start of follow up and stratified by center Breast cancer with and without RRSO (+/-HRT)

10. BRCA1/2 Mutation carriers in the US nCarriers Non-Jewish (1/350) 294,985,491842,816 Jewish (1/40) 6,635,665165,892 Total301,621,1571,008,707 ~1,000,000 BRCA1/2 carriers

11. BRCA1/2 Mutation carriers in the US Females 20 and above between 1996 and today Close to 500,000 BRCA1/2 carriers PopulationCarriers Non-Jewish (1/350) 145,175,175414,786 Jewish (1/40) 311,407477,852 Total 148,289,249 492,638

12. 16 years of genetic testing: BRCA1/2 carriers found to date ~60,000 (12%) of the ~500,000 carriers BUT Most people tested already have cancer Estimate that 95% of unafffected carriers remain unidentified

13. Mammography in the 1970’s Patient presents with obvious cancer

14. Mammography in the 1970’s Patient presents with obvious cancer Mammogram shows obvious cancer Minimal impact on population health

15. Mammography today Major impact on population health Millions of screening mammograms Tens of thousands of subclinical cancers identified

16. Risk identification today Age 35 presents with obvious cancer

17. Risk identification today Age 35 presents with obvious cancer Pedigree shows obvious hereditary syndrome Minimal impact on population health

18. Risk Assessment Tomorrow Major impact on population health Millions of family histories collected and assessed Hundreds of thousands of high risk patients identified Tens of thousands of cancers prevented or found earlier

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

20. 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

21. NCCN 2011, Genetic Testing

22. Know models or use a computer BRCAPRO: Bayes-Mendel Model

23. Data entry to do one computer model

24. Clinician synthesizes patient data, compares to guidelines/models, determines next steps Who is at risk

25. Dependant on paper form

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

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

28. 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

29. HughesRiskApps.Net Patient enters data into Tablet PC or iPad Flag for risk assessment Patient educational materials Clinical Decision Support

30. Newton Wellesley Hospital Since 4/2007 Over 50,000 unique patients 2255 (4.5%) mutation risk 10% or greater

31. Not Jewish No Cancer Jewish No Cancer Not Jewish Cancer Jewish Cancer Mammography patients needing risk assessment

32. Demo

33. DISCLOSURES HughesRiskApps.Net Open Access Solution http://www.HughesRiskApps.com kshughes@partners.org http://www.HughesRiskApps.com kshughes@partners.org

34. Version 3

36. Monitor uptake on counseling

38. Simplify Contact

39. Simplify contact and record outcome

40. If patient declines, record reason

41. Module

43. Average EHR today CDS

44. Average EHR today Click open 4 screens

45. Average EHR today, poor CDS