1. Breast Cancer 2010 David B. Pearlstone, MD MBA FACS Co-Director, Breast Division John Theurer Cancer Center Chief, Division of Breast Surgery Hackensack University Medical Center

2. Outline – Epidemiology – Screening – Work up Genomics or ‘personalized medicine’ – diagnosis and treatment – breast & ovarian cancer

4. Breast Cancer 101 Statistics Most commonly diagnosed cancer among women; 27% of all cancers diagnosed in women are breast cancers. Second most common cause of cancer deaths among women, after lung cancer; 15% of all women who die of cancer, die of breast cancer.

5. Incidence of Cancers Among Women Jemal et al, Cancer Statistics, 2009 CA Cancer J Clin 2009;59:225

6. Cancer Deaths Among Women Jemal et al, Cancer Statistics, 2009 CA Cancer J Clin 2009;59:225

7. Cancer Cases and Cancer Deaths “Find more, Die less” Jemal et al, Cancer Statistics, 2009 CA Cancer J Clin 2009;59:225

9. Breast Cancer 101 Biology any cell can produce malignancy – glandular/ductal cells – high turnover – Adenocarcinomas ductal adenocarcinoma, ‘garden variety breast cancer’

10. ACS Screening Recommendations Women should know how their breasts normally feel and report any breast change promptly to their health care providers. Breast self-exam (BSE) is an option for women starting in their 20s. Yearly mammograms are recommended starting at age 40 and continuing for as long as a woman is in good health. Women at high risk (greater than 20% lifetime risk) should get an MRI and a mammogram every year. Women at moderately increased risk (15% to 20% lifetime risk) should talk with their doctors about the benefits and limitations of adding MRI screening to their yearly mammogram. Yearly MRI screening is not recommended for women whose lifetime risk of breast cancer is less than 15%. Clinical breast exam (CBE) should be part of a periodic health exam, about every 3 years for women in their 20s and 30s and every year for women 40 and over. http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_ Cancer_Detection_Guidelines_36.asp?sitearea=PED

11. Breast Self Exam Women should know how their breasts normally feel and report any breast change promptly to their health care providers. Breast self-exam (BSE) is an option for women starting in their 20s. Monthly – Cycle – Shower

12. Breast Self Exam Don’t be intimidated You know yourself better than you think you do

14. Breast Imaging Mammography Ultrasound MRI Microwave imaging Thermography Electroimpedence

15. Breast Imaging Mammography 40 mammogram Yearly mammograms are recommended starting at age 40 and continuing for as long as a woman is in good health. Exceptions personal history strong family history Role of ultrasound in early screening Evolving field

16. Breast Imaging MRI Women at high risk (greater than 20% lifetime risk) should get an MRI and a mammogram every year. Women at moderately increased risk (15% to 20% lifetime risk) should talk with their doctors about the benefits and limitations of adding MRI screening to their yearly mammogram. Yearly MRI screening is not recommended for women whose lifetime risk of breast cancer is less than 15%.

17. Annual Exam Clinical breast exam (CBE) should be part of a periodic health exam, about every 3 years for women in their 20s and 30s and every year for women 40 and over.

19. Annual Exam History symptoms (mass, pain, discharge, skin changes), gyn history, family history, endocrine therapy history PERSONAL HISTORY OF BREAST CANCER Physical visual v. palpable, skin changes, nipple, axilla/supraclavicular Imaging

20. Annual Exam Genetics consultation/discussion Analysis of risk Risk reduction

21. The Dread “Finding” “I think you should see a breast specialist.” Work up Biopsy FNA core needle excisional palpable wire localized ~80% negative rate

23. Genomics Diagnosis BRCA1 & BRCA2 other genotypes treatment options – observation – medical – surgical FAMILY HISTORY – Most breast cancers are sporadic – Few are familial – Even fewer are ‘genetic’ – IF YOU DON’T HAVE THE MUTATION, YOU ARE NOT OFF THE HOOK

24. Genomics Breast Cancer Risk with BRCA Mutation 12 % of women in the general population will develop breast cancer sometime during their lives 60% of women who have inherited a harmful mutation in BRCA1 or BRCA2 will develop breast cancer sometime during their lives. In other words, a woman who has inherited a harmful mutation in BRCA1 or BRCA2 is about five times more likely to develop breast cancer than a woman who does not have such a mutation.

25. Genomics BRCA1 &BRCA2 Tumor suppressor genes Not just breast cancer BRCA1: cervical, uterine, pancreas, colon cancer male breast cancer, testicular, prostate BRCA2: pancreas, stomach, gall bladder, melanoma

27. Genomics BRCA1 &BRCA2 The BRCA1 gene is located on the long (q) arm of chromosome 17 at band 21, from base pair 38,449,840 to base pair 38,530,994 The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3), from base pair 31,787,616 to base pair 31,871,804

28. Genomics BRCA1

29. Genomics BRCA1 & BRCA2 Certain variations of the BRCA1 gene lead to an increased risk for breast cancer. Researchers have identified hundreds of mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer. Women who have an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70; increased risk of developing ovarian cancer is about 55% for women with BRCA1 mutations and about 25% for women with BRCA2 mutations

30. Genomics Who is most likely to have a BRCA mutation? Three specific mutations, two in the BRCA1 gene and one in the BRCA2 gene, are the most common mutations found in these genes in the Ashkenazi Jewish population. In one study, 2.3 percent of participants (120 out of 5,318) carried one of these three mutations This frequency is about five times higher than that found in the general population. Norwegian, Dutch, and Icelandic peoples, also have higher frequencies of specific BRCA1 and BRCA2 mutations. Frequencies of specific BRCA1 and BRCA2 mutations may vary among individual racial and ethnic groups in the United States, including African Americans, Hispanics, Asian Americans, and non-Hispanic whites.

32. Genomics Who Should Get BRCA Tested? – For women who are not of Ashkenazi Jewish descent: two first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was diagnosed at age 50 or younger; three or more first-degree or second-degree (grandmother or aunt) relatives diagnosed with breast cancer regardless of their age at diagnosis; a combination of first- and second-degree relatives diagnosed with breast cancer and ovarian cancer (one cancer type per person); a first-degree relative with cancer diagnosed in both breasts (bilateral breast cancer); a combination of two or more first- or second-degree relatives diagnosed with ovarian cancer regardless of age at diagnosis; a first- or second-degree relative diagnosed with both breast and ovarian cancer regardless of age at diagnosis; and breast cancer diagnosed in a male relative.

33. Genomics Who Should Get BRCA Tested? – For women of Ashkenazi Jewish descent: any first-degree relative diagnosed with breast or ovarian cancer; and two second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer. DO YOU REALLY WANT TO BE TESTED?

34. Genomics Genetic Discrimination GINA – Enacted 2008 – protect U.S. citizens against discrimination based on their genetic information in relation to health insurance and employment. – The parts of the law relating to health insurers will take effect between May 2009 and May 2010 – The parts relating to employers will take effect by November 2009. – does not cover life insurance, disability insurance, and long-term care insurance. – does not cover members of the military.

35. Genomics Genetic Discrimination Some of the protections under GINA with regard to health insurance include the following: – Premiums or contributions to a group health plan cannot be increased based on the genetic information of an individual(s) enrolled in the plan. – Insurers cannot require an individual or family member to undergo a genetic test before enrollment in a group health plan. – Insurers cannot request, require, or purchase genetic information about an individual before the person’s enrollment in a group health plan – Health insurers cannot use genetic information as the only basis upon which to claim a pre-existing condition is present and, therefore, to deny coverage.

36. Genomics Genetic Discrimination Some of the protections under GINA with regard to employment include the following: – Employers cannot refuse to hire and cannot fire individuals based on their genetic information. – Employers cannot discriminate against employees because of their genetic information. – Employers cannot request, require, or purchase genetic information about an employee except under specific circumstances. – Employers cannot disclose an employee's genetic information except under specific circumstances.

38. Genomics BRCA & Ovarian Cancer 1.4 % of women in the general population will be diagnosed with ovarian cancer 15 to 40 % of women who have a BRCA1 or BRCA2 mutation will be diagnosed with ovarian cancer.

39. Genomics Other Genetic Mutations Mutations in several other genes, including TP53, PTEN, STK11/LKB1, CDH1, CHEK2, ATM, MLH1, and MSH2, have been associated with hereditary breast and/or ovarian tumors. The majority of hereditary breast cancers can be accounted for by inherited mutations in BRCA1 and BRCA2. Overall, it has been estimated that inherited BRCA1 and BRCA2 mutations account for 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers among white women in the United States

40. Genomics Myriad Genetics BRCA1 and BRCA2 are patented in the United States by Myriad Genetics This US patent has been challenged by the American Civil Liberties Union

41. Breast Cancer & You Monthly breast self exam Annual practitioner exam Annual mammogram Know your family history BE PROACTIVE

43. Breast Cancer 2010 David B. Pearlstone, MD MBA FACS Co-Director, Breast Division John Theurer Cancer Center Chief, Division of Breast Surgery Hackensack University Medical Center