Kevin S.Hughes, MD, FACS Co-Director, Avon Comprehensive Breast Evaluation Center Massachusetts General Hospital Surgeon

1. High Risk Gene Profiles in Breast Cancer Management Genetic Risk Factors in Primary Management of Breast and Colorectal Cancer Tuesday, April 3, 2012 Crowne Plaza Hotel at the Crossings Kevin S.Hughes, MD, FACS Co-Director, Avon Comprehensive Breast Evaluation Center Massachusetts General Hospital Surgeon The Newton-Wellesley Hospital Breast Center

2. DISCLOSURESHughesRiskApps.NetOpen Access Solutionhttp://www.HughesRiskApps.comSpeaker’s BureauMyriad Geneticskshughes@partners.org

3. Inherited Susceptibility to Breast Cancer Sporadic Genetic Component (~29%) BRCA1 BRCA2 CHK2 ATM p53 PTEN p16 LKB1 Unknown Courtesy David Euhus, MD

4. Li-Fraumeni (p53) Clinical Features • Early onset breast, sarcoma, leukemia, CNS, adrenal cortical, lung, melanoma, pancreas, cervix, prostate. • Breast most common • Very early onset (20’s) Courtesy David Euhus, MD

5. Peutz-Jegher Syndrome (LKB1) Clinical Features • Gastrointestinal hamartomatous polyps • Melanin pigmentation of lips and mouth • Small bowel cancers • Colorectal cancer • Pancreas, ovary, endometrium, cervix, lung, testicle • Cancer risk 47% by age 65 • Early onset breast cancer (RR = 5) Courtesy David Euhus, MD Lim W, Brit J Cancer 2003;89:308-313

6. Diffuse Gastric Cancer (CDH1) • Infiltrating lobular breast cancer • Lifetime risk 39% • Diffuse gastric cancer • Lifetime risk 67 – 83% (F>M) • Mean age 38 • Earliest age 14 Courtesy David Euhus, MD

7. Cowden Syndrome (PTEN) Clinical Features • Facial trichilemmomas • Macrocephaly (> 58 cm) • Oral papules • Benign and malignant thyroid disease (10%) • Endometrial Cancer • Hamartomatous ileal and colonic polyps • Breast cancer risk 30 – 50% • Male breast cancer • Benign Breast Disease • adenosis or lobular atrophy • hamartoma • fibrosis • fibroadenoma Courtesy David Euhus, MD Schrager CA, Human Pathol 1998;29:47-53

8. Cancer Risk BRCA1BRCA2 F e m a l e M a l e Breast 50-87% 50-87% Ovary 40-60% 10-20% Breast 6%

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

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

11. Options for high risk

13. Options for high risk Chemoprevention Prophylactic Oophorectomy Screening

14. Breast cancer with and without RRSO (+/-HRT) Adjusted for age at start of follow up and stratified by center

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

16. BRCA1/2 Mutation carriers in the USFemales 20 and above Close to 400,000 BRCA1/2 carriers

17. 13 years of genetic testing: BRCA1/2 carriers found to date • ~20,000 to 30,000 • 2 to 3% of the ~1,000,000 carriers

18. BRCA1/214 years of genetic testing We have identified about 60,000 of the estimated 1,000,000 carriers in the U.S. Likely the best of any adult hereditary syndrome

19. Find all mutation carriers Family history & selective testing Population based genetic testing 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 Personal History Family History Ethnicity Genetic Testing Who is at risk

25. Dependant on paper form

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

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

28. Average EHR today CDS

29. Average EHR today Click open 4 screens

30. Average EHR today

31. 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

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

33. Monitor uptake on counseling

34. Newton Wellesley HospitalSince 4/2007 • Over 50,000 unique patients • 2255 (4.5%) mutation risk 10% or greater

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

36. DISCLOSURESHughesRiskApps.NetOpen Access Solutionhttp://www.HughesRiskApps.comkshughes@partners.org

37. Demo

39. Simplify Contact

40. Simplify contact and record outcome

41. If patient declines, record reason

42. Module