1. What’s new in Breast Disease M. Whitney Parnell MD FACS Surgical Associates of Myrtle Beach Breast and General Surgery

2.  Dense Breasts  ABUS  3-D Mammography  BRCA1 BRCA2 and beyond  Prophylactic Surgery  Cancer Sub-typing (oncotype DX/Mammoprint) Hot topics

3. What does it mean to say dense breasts? Who has dense breasts? Are women with dense breasts at increased risk of developing cancer? What should we do differently? Legislation Dense Breasts

4. Breast Anatomy  Fat and glandular tissue  More glandular tissue=denser breast  Denser the breasts the whiter the mammogram  Mammogram may miss up to 40% of cancers in dense breasts

5. Dense Breasts  Age  Hormone levels  Genetics  Age at first pregnancy  #of pregnancies  HRT

6. Mammograpy’s dirty little secret  Up to 40% of cancer can be missed on standard mammography in dense breasts !

7.  Type 1—mostly fatty replaced  Type 2 Average breast tissue 25-50%  Type 3 Heterogenously dense 50-75%  Type 4 Extremely dense >75% dense tissue Dense breast Classifications

8. Dense Breast Classifications

10. Why Mammography?  Inexpensive  Safe (low radiation)  Accessible  Sensitive and Specific  Effective in reducing mortality from Breast Cancer  Since 1990’s there has been a decrease in mortality from breast cancer 2.2%/year due to screening mammography

11.  Most frequent dx non-skin cancer in Women  226,870 new cases/yr in US  63,000 new cases of DCIS  40,000 women die annually of breast cancer  Second leading cause of cancer death in women Breast Cancer Stats

12. Breast Cancer Risk Factors  Early menarche  Late Menopause  Nulliparous  HRT  Post-menopausal obesity  ETOH  Breast Density

13.  Dense breast are an independent risk cancer for cancer development  Mult retrospective studies show the odds ratios for developing breast cancer in the least dense compared with the densest breast ranges from 1.9-6.0 (ave 4.0)  Harvey et al. Radiology 2004 Dense breasts=more Cancer?

14.  Breast cancer is a progressive disease and early detection offers women an opportunity to halt the natural evolution of the cancer, increases her treatment options, and ultimately saves lives. Early Detection

15.  Mammogram is still the gold standard for screening and it is an invaluable tool—  Assessing interval change  Architectural distortions  Calcifications (i.e. DCIS—stage 0) Why get a mammogram if I have dense breasts?

17.  Breast Ultrasound  MRI  Digital breast tomosynthesis Other Imaging Modalities

18.  Safe—no radiation  Technologic advancements have improved resolution  Breast density is a non-issue  Easy to perform  Well tolerated by patient  Invaluable asset to mammography Ultrasound

19.  High risk women with dense breasts  Improved cancer detection 13-28%  Most cancers were early stage invasive node negative cancer  Kolbe et al Radiology 2002  ACRIN 6666; JAMA 2008 Improved Cancer Detection

20.  Connecticut was first 2009—Public Act 09-41  "If your mammogram demonstrates that you have dense breast tissue, which could hide small abnormalities, you might benefit from supplementary screening tests, which can include a breast ultrasound screening or a breast MRI examination, or both, depending on your individual risk factors. A report of your mammography results, which contains information about your breast density, has been sent to your physician's office and you should contact your physician if you have any questions or concerns about this report. Legislation

21.  First year experience with the new law requiring all women with dense breasts to be screened with u/s along with the mammogra  935 women; 5% had suspicious u/s—bx  PPV was 6.5%  Overall cancer detection rate 3.2/1000  Hooley et al. Screening US in patients with Mammographically dense breasts: Initial Experience with Connecticut Public Act 09-41  Radiology; 2012 265:59-69 Connecticut

23. South Carolina  Introduce bill Feb 2013  Currently in the House Committee on Labor Commerce and Industry  Sponsored by Senator Joel Lourie

24.  Staffing/Time intensive with low reimbursement  Technician dependent  ACR/ACS lack guidelines  Adding u/s to mammography increases the false positive rate 4X— ACRIN 6666: Jama 2008 Breast Ultrasound

26.  Automated Breast Ultrasound Screening  3mins per breast (19mins with u/s tech)  Full exam time 15 mins  Gives complete 3-D volumetric imaging of the breast  Approved in Sept 2012 “explicitly for breast cancer screening for asymptomatic women with dense breast tissue.”  97% sensitive when used with mammograpy ABUS

29.  ACS guidelines Recommended for high risk individuals annually with mammography  Known BRCA 1 or 2 mutations  First degree family member with genetic mutation  >20% lifetime risk based on Risk analysis models  Chest wall radiation ages 10-30  Li-Fraumeni, Cowden and Bannayan-Riely Ruvalcaba syndromes and first degree relatives Breast MRI

30.  Expensive  Requires contrast agent (baseline creatinine)  Uncomfortable (prone position)  Lacks insurance mandate  Lacks specificity  Time in the magnet Breast MRI

34.  Originally approved as add-on only  FDA 2013-approved for use without standard 2-D mammography  Provides images of the breast in “slices” from many different angles  Not always covered by insurance  Machines cost 2x as much 3-D Mammography

35.  Higher cancer detection rate 4.1 vs 2.9/1000  Less call backs 91 vs 107/1000  Higher bx rate 19.3 vs 18.1  Higher radiation dose (both within safe limits)  Overseas use since 2008—restrict it to patients with breast problems  JAMA. 2014;311(24):2499-2507 3-D Mammography

37.  BRCA1 and BRCA 2 are human genes that produce tumor suppressor proteins  Help repair damaged DNA  With mutations of these genes—damaged DNA is not repaired properly  Responsible for 25% of genetic breast cancer  5-10% of all breast cancer  15% of ovarian cancer Genetics

38. BRCA1  55-65% will develop breast cancer in their lifetime  40% lifetime risk of ovarian cancer  Fallopian tube and peritoneal cancer  Prostate cancer  Pancreatic cancer BRCA2  45% will develop breast cancer in their lifetime  12% lifetime risk of ovarian caner  Linked with male breast cancer  Prostate cancer  Pancreatic cancer

39. Who should get tested?  Breast cancer before 50  Cancer in both breasts  Breast and ovarian cancer  Personal or family hx of Male breast cancer  Triple negative breast cancer before age 60  Ashkenazi Jewish heritage and family hx of breast or ovarian cancer  Ovarian cancer before 50

40. 3 rules  Multiple –combination of cancers in the same side of the family  Young --<50  Rare —male breast; triple neg; colorectal or endometrial cancer with abnormal MSI/IHC;

41.  Identifies elevated risk of 8 cancers by analyzing multiple clincally actionable genes  Retrospective analysis of patients (2006-2013)  6.9% of patients appropriate for HBOC testing also meet Lynch criteria  30% of patients appropriate for Lynch testing also meet HBOC Expanded panel testing

43.  Previvor - "Cancer previvors" are individuals who are survivors of a predisposition to cancer but who haven’t had the disease. This group includes people who carry a hereditary mutation, a family history of cancer, or some other predisposing factor.  Unaffected carrier Previvor

44.  Increased awareness  Increased inquiries into testing  Better lay understanding of genetic testing  Prophylactic Mastectomy Angelina Jolie Effect

45.  Risk reduction of 90+ %  Still need to consider prophylactic oophorectomy  Nipple sparing techniques (1% less risk reduction) Prophylactic Mastectomy

48. Molecular profiling  Oncotype Dx  Mammoprint

49.  Genomic test of the activity of a group of genes  How cancer may respond to treatment  Early stage ER+ breast cancer recurrence and ?benefit from chemo  DCIS—recurrence and or risk of new invasive cancer developing and ?benefit from XRT OncotypeDX

51. Summary  Dense breasts Birads 3 and 4 benefit from annnual screening ultrasound  Consider genetic testing for multiple/ young/rare  Nipple sparing prophylatic mastectomy option  Cancer molecular profiling or subtyping expanding—targeted therapy

53. Questions? Questions