1. Breast Cancer Adapted From: SEER’s Training Web Site http://training.seer.cancer.gov.index.html MCR Staff Supported by a Cooperative Agreement between DHSS and the Centers for Disease Control and Prevention (CDC) and a Surveillance Contract between DHSS and MU

2. Background  Excluding cancers of the skin, breast cancer is the most common type of cancer in women in the United States. Accounts for one of every three cancer diagnoses.  An estimated 174,480 new invasive cases of breast cancer were expected to occur among women in the United States during 2007.  About 2,030 new male cases of breast cancer were expected in 2007.

3. Background  The incidence of breast cancer rises after age 40. highest incidence (approximately 80% of invasive cases) occurs in women over age 50.  62,030 new cases of in situ breast cancer were expected to occur among women during 2007.  Approximately 88% will be classified as ductal carcinoma in situ (DCIS).

4. Background  2007 - estimated 40,910 deaths (40,460 women, 450 men)  Ranks second among cancer deaths in women.  Mortality rates steadily decreased since 1990 Larger decrease in women under 50 Due to combination of earlier detection & improved treatment

5. Five-Year Survival Rates (ACS Relative) Stage 0100% Stage I100% Stage IIA92% Stage IIB81% Stage IIA67% Stage IIIB54% Stage IV20% http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_breast_cancer_staged_5.asp 9/13/2007

6. Risk Factors  Age—more prevalent in older women  Exposure to natural estrogens First childbirth after age 30 Age at menopause Obesity—estrogens stored in body fat  Affluence High-fat diet Alcohol consumption  Genetics/family history

7. Reducing Risk  Having children at early age  Breast feeding  Healthy body weight  Exercise  Anti-estrogens

8. Symptoms  New lump or mass painless, hard, uneven edges sometimes tender, soft, or rounded  Swelling  Skin irritation or dimpling  Nipple pain or nipple turning inward  Redness or scaliness of the nipple or breast skin  Nipple discharge (other than milk)  A lump in the underarm area

9. Breast Anatomy  Breast Made up of milk-producing glands Supported and attached to the chest wall by ligaments Rests on pectoralis major muscle No muscle tissue Layer of fat surrounds the glands and extends throughout breast  Three major hormones affect the breast Estrogen, progesterone, and prolactin

10. Breast Anatomy

11.  Breast contains 15–20 lobes  Fat covers the lobes and shapes the breast  Lobules fill each lobe  Sacs at the end of lobules produce milk  Ducts deliver milk to the nipple

12. Anatomy – the lymphatic system  Important to know if cancer has spread to the lymph nodes  The more nodes involved, the more likely it is that the cancer may involve other organs.  Affects treatment plan.

13. Anatomy – the lymphatic system Most lymphatic vessels in the breast connect to lymph nodes under the arm (axillary) Also internal mammary nodes Supraclavicular or infraclavicular nodes

14. Types of Breast Cancer  The earliest form of the disease is ductal carcinoma in situ, comprises about 15-20% of all breast cancers and develops solely in the milk ducts.  Invasive ductal carcinoma, develops from ductal carcinoma in situ, spreads through the duct walls, and invades the breast tissue. Most common – 70-80% of cases

15. Types of Breast Cancer cont’d.  Cancer that begins in the lobes or lobules is called lobular carcinoma. more likely to be found in both breasts. accounts for 10–15% of invasive breast cancers.  Both ductal and lobular carcinomas can be either in situ, or self-contained; or infiltrating, meaning penetrating the wall of the duct or lobe and spreading to adjacent tissue.

16. Types of Breast Cancer cont’d.  Less common types of breast cancer include the following: Inflammatory Medullary carcinoma (originates in central breast tissue) Mucinous carcinoma (invasive; usually occurs in postmenopausal women) Paget disease of the nipple Phyllodes tumor (tumor with a leaf-like appearance that extends into the ducts; rarely metastasizes) and Tubular carcinoma (small tumor that is often undetectable by palpation)

17. Inflammatory Carcinoma  frequently involves entire breast  characterized by reddened skin and edema caused by tumor spread to lymphatic channels of skin of breast  usually without an underlying palpable mass  Is a clinical diagnosis verified by biopsy of the tumor and overlying skin.  Key words: lymphatic involvement of skin, peau d'orange, orange-peel skin, en cuirasse Image source: National Cancer Institute

18. Paget’s disease  Crusty tumor of nipple and areola, which may be associated with underlying tumor of the ducts. www.sunmed.org/cbesk2.jpg

19. DCIS  In Situ: Abnormal cells that have not escaped the part of the body where they developed  For Breast – abnormal cells in the lining of a milk duct that have not invaded surrounding breast tissue  Appearance of being precancerous when viewed under a microscope, but  No ability to spread as cancer cells would  After DCIS, increased risk of invasive breast cancer from 2 to more than 8 times higher than the risk found in general population

20. Behavior  Invasive (infiltrating)  In situ (15-20% of all breast cancers)  Synonyms for carcinoma in situ: noninfiltrating, intraductal, lobular carcinoma in situ, Stage 0, TIS noninvasive, no stromal involvement, papillary intraductal, papillary non infiltrating, intracystic, lobular neoplasia, lobular noninfiltrating, confined to epithelium, intraepithelial, intraepidermal, DCIS, LCIS

21. Grade (differentiation)  Assigned by pathologist  How close does the bx resemble normal tissue  Helps predict prognosis  Lower number indicates slower-growing cancer that is less likely to spread  Higher number indicates a faster-growing cancer that is more likely to spread

22. Grades  Grade 1 (well differentiated) cancers have relatively normal-looking cells that do not appear to be growing rapidly and are arranged in small tubules.  Grade 2 (moderately differentiated) cancers have features between grades 1 and 3.  Grade 3 (poorly differentiated) cancers, the highest grade, lack normal features and tend to grow and spread more aggressively

24. Grade: Bloom-Richardson  Bloom-Richardson (BR) Score Frequency of cell mitosis Tubule formation Nuclear pleomorphism  Bloom-Richardson Grade Low grade = BR score 3–5 = grade 1 Intermediate grade = BR score 6, 7 = grade 2 High grade = BR score 8, 9 = grade 3

25. Diagnosing Breast Cancer  Mammogram  MRI  Ultrasound  Biopsy Fine Needle Aspiration Core Needle Biopsy (stereotactic and other) Excisional biopsy (sometimes with wire localization)  Lymph node dissection and Sentinel lymph node biopsy

26. Sentinel Lymph Node Biopsy A.D.A.M. illustration used with licensed permission.

27. Breast Cancer Staging (TNM) StageTumor (T)Node (N)Metastasis (M) Stage 0TisN0M0 Stage 1T1N0M0 Stage IIA T0N1M0 T1N1M0 T2N0M0 Stage IIB T2N1M0 T3N0M0 Stage IIIA T0N2M0 T1N2M0 T2N2M0 T3N1, N2M0 Stage IIIB T4any NM0 any TN3M0 Stage IVany Tany NM1 Source: American Joint Commission on Cancer and International Union Against Cancer

28. Treatment  Surgery Mastectomy Lumpectomy Removal of axillary lymph nodes (for invasive cancers)  Sentinel node biopsy  Axillary dissection  Radiation Usually after surgery  Chemotherapy Combinations of drugs  Hormone therapy Tamoxifen, others

29. Estrogen & Progesterone Receptor Status  Proteins on the surface of cells that can attach to substances such as hormones, that circulate in the blood.  Normal breast cells & some breast cancer cells have receptors that attach to estrogen and progesterone.  Play a role in the growth and treatment of breast cancer.  ER-positive tumors have a better prognosis and are more likely to respond to hormone therapy  About 2/3 breast ca contain at least one of these  Higher percentage in older women

30. Premenopausal: Tamoxifen  Ovaries produce estrogen, sent through bloodstream directly to the breast  Tamoxifen mimics estrogen  Attached to receptors, keeping real hormones out

31. Postmenopausal: Aromatase inhibitors  Produce most of their estrogen outside the ovaries  Generated through androgen hormones store in fatty tissue and adrenal glands  In a biochemical process started by the enzyme aromatase, androgen is converted into estrogen, into bloodstream and to breast  Aromatase inhibitors “block” the process

32. Aromatase Inhibitors (AIs)  Steroidal AIs Aromasin (exemestane)  Nonsteroidal AIs  Arimidex (anastrazole)  Femara (letrozole)  Many clinical trials showing significant results in both reduced breast cancer relapse, as well as reduced rates of metastatic disease  Now being studied in various scenarios with Tamoxifen

33. HER2/neu Status  human epidermal growth factor receptor 2  A protein involved in normal cell growth  Important in the control of abnormal or defective cells that could become cancerous  HER2/neu positive cancers have an excessive amount of the HER2/neu cancer gene protein in and around their cells.

34. Herceptin  Considered a targeted therapy or an immune treatment  Given IV, once every 2-3 weeks  Targets the HER2 protein production  Helps stop the growth of the HER2 positive cancer cells  Helps prevent recurrence  http://www.cancer.gov/cancertopics/factsheet/therapy/herceptin http://www.cancer.gov/cancertopics/factsheet/therapy/herceptin

35. Tests for HER2 Breast Cancer  IHC: ImmunoHistoChemistry – measures the production of the protein by the tumor. Ranked as 0, 1+, 2+ or 3+ 3+ = HER2 positive cancer  FISH: Fluorescence In Situ Hybridization – probes to look at the number of HER2 gene copies in the tumor cell.

36. Treatment Options are changing  Intraductal (in situ) – no longer recommend total mastectomy (recent)  Treatment options may vary with age Brachytherapy (mammosite)  Patients >45 or >50  Node negative  Small tumors  Combinations of tamoxifen/AIs  Avastin – new class of drug Blocks formation of blood vessels that supply tumors

37. Missouri Cancer Registry Help Line: 800-392-2829 Help interpreting path report for staging http://mcr.umh.edu  For further information, please contact: Sue Vest, Project Manager vests@health.missouri.eduvests@health.missouri.edu Nancy Cole, Assistant Project Manager colen@health.missouri.edu