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 of Breast Cancer

2. Saslow D et. al. CA Cancer J Clin 2007; 57: 75

3. ACS MRI Guidelines Saslow D et. al. CA Cancer J Clin 2007; 57: 75

4. 10,000 4/1/2006 to 9/17/2007 7,821 NULL or No Never HORMONES 6,981 W/ Gail Score 6,028 W/ BRCAPRO Lifetime 5,894 W/ BRCAPRO Mutation and Tyrer-Cuzick LCIS/AH status not available

5. ACS MRI Guidelines Exclude Gail Model …less useful than BRCAPro, Claus, and Tyrer-Cuzick …not adequate for evaluating family history Therefore we do not recommend its use for evaluating patients for breast MRI screening Online Supplemental Material

6. ACS Guidelines Saslow D et. al. CA Cancer J Clin 2007; 57: 75 BRCAPRO Tyrer-Cuzick Claus Gail

7. ACS Guidelines Claus Breast FH BRCAPRO Breast and ovarian FH Tyrer-Cuzick Breast and ovarian FH Pathologic factors Hormonal factors

8. Tyrer-Cuzick= 330 (5.6%) 276 BRCAPRO = 25 (0.4%) Claus = 54 (0.9%) 10 2 31 13 0 10 Lifetime Breast Cancer Risk 20% or greater by Model

9. 20 to 25% LT Risk of…What? Invasive cancer –BRCAPRO Invasive plus DCIS –Claus –Tyrer-Cuzick

10. Tyrer-Cuzick= 330 (5.6%) 263 Claus = 54 (0.9%) 23 19 26 18 1 9 Lifetime Breast Cancer Risk 20% or greater by Model Adjusted BRCAPRO 61 (1%)

11. ACS MRI Guidelines Saslow D et. al. CA Cancer J Clin 2007; 57: 75 LCIS/AH

12. 20% or greater lifetime risk –Any LCIS age 69 and below –Any AH age 56 and below Tyrer Cuzick for AH & LCIS Even more with even trivial risk factors

13. IDing patients for MRI is not enough Need complete risk assessment Genetic testing as appropriate Manage Breast and Ovarian Risk! Consider Genetic Testing if Risk Mutation is 10% or greater

14. Better Strategy Identify mutation carriers (genetic testing) –MRI for those with mutation (selective MRI) –Offer ALL risk reducing strategies Oophorectomy Prophylactic mastectomy MRI Mammography

15. Avon Comprehensive Breast Center Database 18,190 screening mammogram patients 40 or older –(May 2003 – July 2005) –BRCAPRO run on all

16. Avon Comprehensive Breast Center Database Lifetime risk ≥20% 78 (0.4%) 18,190 screening mammogram patients 40 or older –(May 2003 – July 2005) –BRCAPRO run on all

17. Avon Comprehensive Breast Center Database Lifetime risk ≥20% 78 (0.4%) Predicted Mutation Carriers 27 BRCAPRO 18,190 screening mammogram patients 40 or older –(May 2003 – July 2005) –BRCAPRO run on all

18. Avon Comprehensive Breast Center Database 374 (2.1%) Mutation Risk ≥10% Lifetime Risk <20% and 18,190 screening mammogram patients 40 or older –(May 2003 – July 2005) –BRCAPRO run on all

19. Avon Comprehensive Breast Center Database 374 (2.1%) Predicted Mutation Carriers 62 BRCAPRO Mutation Risk ≥10% Lifetime Risk <20% and 18,190 screening mammogram patients 40 or older –(May 2003 – July 2005) –BRCAPRO run on all

20. MGH Screening Data: All Comers Risk of Mutation Risk of Breast Cancer n Mean Probability of Mutation Projected # Mutation Carriers ≥10%≥20%780.3427 ≥10%<20%3740.1762

21. What to do ≥10% risk of mutation –Genetic testing Positive-Manage with all modalities Negative-Your call –Based on FH

22. Options for high risk

23. Prophylactic Oophorectomy Screening Chemoprevention Options for high risk

24. Conclusions ≥10% risk of mutation –Genetic testing Positive-Manage with all modalities Negative-Your call –Depend on FH ≥20% LT Risk –Lots by TC –Almost all LCIS and AH by TC –Do they all need MRI?

25. Kshughes@Partners.org www.HughesRiskApps.net