1. Breast MR Imaging Workshop 2014 13 th September 2014 High-Risk Screening Evidence-based Clinical Indications for Breast MRI Dr. Muhamad Zabidi Ahmad, AMDI

2. Introduction Worldwide in 2010, estimated 1,643,000 new cases of breast cancer 1. 60% of breast cancer deaths are from less developed nations 2. Increased screening program in 1990’s has led to early detection. Mainly by mammogram and/or ultrasound. 1.Jemal et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69. 2.World Health Organization. Breast cancer: Prevention and Control

3. Strategies for Screening Take into account the combined evidence for risk of breast cancer and effectiveness and harms of breast cancer screening. Mammogram is mainstay. Role of MRI is emerging – In combination with mammography, targeted to high-risk patients.

4. The Important Points 1 Who are the high-risk group? 2 What are the experts say? 3 In context of our population

5. Who Are The High-risk Group? 1

6. Risk Factors for Developing Breast Cancer Age – risks increases with age Family history Early menarche, late menopause Oral contraceptive use Age at first birth >30 Breast density on mammogram BRCA mutation carrier Alcohol

7. ACS American Cancer Society (2007) 3 recommends annual MRI, in addition to mammogram, to women in these groups: – Known BRCA mutation carriers – First degree relatives of known BRCA carriers – Approximate lifetime risk of breast cancer from 20 to 25 percent based on risk prediction model 3. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.

8. NCCN National Comprehensive Cancer Network (NCCN) 4 recommended annual breast MRI in adjunct to mammography in these groups: – BRCA1 and BRCA2 mutation carriers – First degree relative with BRCA1 or BRCA2 mutation – Family history of breast or ovarian cancer – Received radiation treatment to the chest between ages 10 and 30 – TP53 or PTEN genes mutation 4. Bevers TB, Anderson BO, Bonaccio E, et al. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis. J Natl Compr Canc Netw 2009; 7:1060.

9. Carriers of BRCA1, BRCA2, or TP53 mutation First degree relative of someone who carries BRCA1, BRCA2, or TP53 mutation Strong family history of breast or ovarian cancer; or both Family history consistent with Li-Fraumeni syndrome* * Li-Fraumeni syndrome – extremely rare AD hereditary disorder. Classical malignancy – sarcomas, cancers of the breast, brain and adrenal glands Received radiation treatment to the chest between ages 10 and 30

10. 2 What Are The Experts Say A look into published literatures

11. No data from randomized control trials that show a benefit of screening by MRI in women with low to average risk of breast cancer. Contributed partly by higher cost of MRI compared to mammography 5. Screening breast MRI is more sensitive but less specific than mammography for detection of invasive breast cancer in high-risk women in both retrospective and prospective studies. 5. http://www.uptodate.com/contents/screening-for-breast-cancer-evidence-for-effectiveness-and- harms?topicKey=PC%2F87311&elapsedTimeMs=0&source=machin%E2%80%A6

12. Morris et al. Retrospective study involving 367 women with high-risk developing breast cancer. Normal mammography findings. Screening MRI performed during 2 year period.

14. Morris et al. Among high-risk women, MRI led to biopsy in 17%. Cancer found in 24% of women undergoing biopsy. 4% from women who had MRI screening.

15. Warner et al. Retrospective study involving 236 high-risk women with BRCA1 and BRCA2 mutation. Underwent mammogram, MRI and ultrasound as well as clinical breast examination. From 1997 – 2003.

17. Warner et al. MRI is more sensitive in detecting breast cancer compared to mammography, ultrasound or clinical breast examination alone in BRCA1 and BRCA2 mutation women.

18. Stoutjesdijk et al. Retrospective study of all MRI and mammographic study between 1994 to 2001. 179 women. MRI more accurate than mammography in annual screening in women with hereditary risk of breast cancer.

19. Lehman et al. Prospective study involving 195 women over 6-month period. BRCA1/BRCA2 carrier in women 25 years old and older.

21. Lehman et al. Screening MR imaging had higher biopsy rate. Helped detect more cancers than either mammography or ultrasound alone.

22. Berg et al. Prospective study to determine cancer detection yield by ultrasound and MRI in women with elevated risk for breast cancer. 2809 women at 21 sites from 2004 to 2006. MRI resulted in higher detection rate.

23. Reviewed 11 studies comparing test performance of screening MRI with mammography in high-risk women. Age ranging 40 to 47 years old.

24. Sensitivity of MRI higher than mammography: 0.77 (95% CI 0.70 – 0.84) versus 0.39 (CI 0.37 – 0.41). Specificity of MRI lower than mammography: 0.86 (CI 0.81 – 0.92) versus 0.95 (CI 0.93 – 0.97). Sensitivity of MRI and mammography together was 0.94 (CI 0.90 – 0.97) and specificity was 0.77 (CI 0.75 – 0.80).

25. However, the cost of running MRI for screening is higher Take longer time Studies looking into more effective and faster MRI acquisition

26. Takes 3 minutes instead of 40 minutes T1 followed by contrast Images substracted into individual first postcontrast subtracted images (FAST) and fused into single MIP image

28. 3 In Context of Our Population

29. Incidence of breast cancer published in National Cancer Registry 2006 was 39.3 per 100,000 population. Most present at late stage. Mammogram prevalence rate of 7.6% (National Health Morbidity Survey 2006). MRI not used widely.

30. CPG 2 nd Edition 2010 on management of breast cancer

33. CPG on Management of Breast Cancer, 2 nd Edition 2010

34. American Cancer Society recommendation for breast MRI screening.

35. Conclusion MRI as a screening tool for high-risk women Valuable adjunct when used together with mammogram Limited resources for large scale screening program

36. Thank you