1. Breast cancer

2. Etiology 1. Increased exposure to estrogens: A)Estradiol-early menarche ( 55) B)Estrone-overweight women C)Xeno-estrogens (contraceptives-increase the risk of breast cancer, cervical cancer and liver cancer, but decrease the risk of endometrial and ovarian cancer) The three major naturally occurring estrogens in women are estroneestrone (E1)-from fatty tissue, ovaries and adrenals estradiolestradiol (E2)-from the ovaries, adrenals and peripheral conversion of E1 estriolestriol (E3)-from placenta and adrenals.

3. Etiology 2. Lack of breast-feeding 3. Smoking 4. Genetic factors: -BRCA1 or BRCA2 mutations* -Lynch syndromes -other yet unidentified genetic risk factors *The estimated lifetime risk of developing breast cancer for women with BRCA1 or BRCA2 mutations is 40% to 85%.

4. Etiology 5. Mouse mammary tumor virus

5. 1. Ductal invasive carcinoma 2. Lobular invasive carcinoma 3. Paget’s disease of the nipple Histological classification of breast cancer-3 main types

6. Detailed histologic classification of breast cancer-not to memorize Carcinoma, NOS (not otherwise specified). Ductal. Intraductal (in situ). Invasive with predominant intraductal component. Invasive, NOS 80% of all breast cancers Comedo. Inflammatory. Medullary with lymphocytic infiltrate. Mucinous (colloid). Papillary. Scirrhous. Tubular. Other. Lobular. In situ. Invasive with predominant in situ component. Invasive. Nipple. Paget disease, NOS. Paget disease with intraductal carcinoma. Paget disease with invasive ductal carcinoma. Undifferentiated carcinoma. Phyllodes tumor. Sarcomas. Primary lymphomas.

7. Diagnosis of breast cancer- inspection and palpation of the breasts and axillae Palpation is best done after the menstrual bleeding, when the breasts are the softest

8. Breast inspection and palpation-click on the video

9. Diagnosis of breast cancer-imaging Main breast imaging procedures: 1.Mammography 2.Ultrasound-for denser breast tissue (younger women, usually <35 yo) 3.MRI- -//-

10. Diagnosis of breast cancer-biopsy Breast tissue sample taking procedures: I.Fine needle aspiration-ABANDONED FOR FINAL DIAGNOSIS II.Core biopsy: 1.Palpation guided core needle biopsy 2.Stereotactic core needle biopsy 3.Ultrasound guided core needle biopsy III. Surgical biopsy 1.Incisional biospy 2.Excisional biopsy

11. Core biopsy needle or TruCut needle-click on the movie

12. Biopsy types-click on the video

13. Diagnosis of breast cancer- additional diagnostic tests 1.Pulmonary radiography (for lung metastases) 2.Abdominal ultrasound (for liver metastases) 3.Bone scintigraphy (for bone metastases)

14. Treatment of breast cancer 1.Surgery 2.Radiation therapy 3.Chemotherapy 4.Hormonal treatment 5.Treatment with biological agents

15. Surgery 1. Modified radical mastectomy with lymphadenectomy 2. Lumpectomy with lymphadenectomy -lumpectomy is appropriate for tumors generally less than 3 cm, except for smaller breasts, when esthetic results cannot be obtained -not suitable for T4 tumors (fixed to the pectoral fascia, skin or inflammatory breast cancer) Lymphadenectomy should be performed excising levels 1 and 2 of axillary lymph nodes

16. Lymphatic drainage of breast cancer

17. Laterally: through the axillary lymph nodes (group 1-2-3 (3=subclavian)) -> supraclavicular lymph nodes Medially: through the internal mammary lymph nodes

18. Sentinel node procedure Allows identification of the first draining lymph node 1.Lymphoscintigraphy (Filtered Sulfur Colloid tagged with the radionuclide Technetium- 99m) 2.Methylene blue dye

19. Radiotherapy Adjuvant after lumpectomy for the remaining breast Adjuvant for the axilla and supraclavicular lymph nodes, if certain risk factors are present

20. Chemotherapy For almost all breast tumors larger than 2 cm Increases cure rates Given neoadjuvantly for large tumors frequently allows for ulterior lumpectomy

21. Hormonal treatment Given for patients with tumors with positive hormone receptors (estrogen and/or progesterone) It needs to be given for more than 5 years 3 main types of hormonal treatments: 1.LHRH receptor agonists 2.Aromatase inhibitors 3.Tamoxifen

22. 1. LHRH (LH releasing hormone) receptor agonists act in the pituitary gland act first as agonists and create an LH surge, but block the LHRH receptors and thus decrease LH secretion and thus ovarian estradiol

23. 2. Aromatase inhibitors Inhibit the formation of estradiol in the ovaries

24. AROMATASE INHIBITORS

25. 3. Tamoxifen Partial antagonist and agonist Antagonist on estrogen receptors from breast tissue Agonist on estrogen receptors from bone=> no osteoporosis is produced as with the first 2 treatments

26. Biologic treatments Herceptin=monoclonal antibody that blocks the HER2/neu growth factor receptor It is over-expressed in aprox. 30% of early breast cancers

27. Reconstructive surgery I. Immediate (at the time of the mastectomy) -musculo-adipose flaps II. Delayed -musculo-adipose flaps -submuscular silicone gel-/saline-filled implants after stretching the overlying tissue with a tissue-expander over a period of weeks/months

28. Follow-up Evidence from randomized trials indicates that periodic follow-up with bone scans, liver sonography, chest x-rays, and blood tests of liver function does not improve survival or quality of life when compared to routine physical examinations. Based on these data, some investigators recommend that acceptable follow-up be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stage I to stage III breast cancer. The risk of a primary breast cancer in the contralateral breast is approximately 1% per year.

29. Screening of breast cancer Screening of breast cancer with mammography decreases breast cancer mortality* For medium risk women: -Mammography from age 40, indefinitely, annually [American Cancer Society American College of Radiology (ACR), Society of Breast Imaging (SBI)] -OR: Mammography age 50->74, biannually [US Preventive Services Task Force (USPSTF) ] For high risk women (BRCA1 or BRCA2 mutation carriers or untested first-degree relatives of a BRCA mutation carrier) : - Mammography from age 30 * 2009 Cochrane review estimated that mammography resulted in a relative risk reduction of death from breast cancer of 15% or an absolute risk reduction of 0.05%

30. Questions 1.Which are the etiologic factors (risk factors) of breast cancer? 2.Which are the steps of diagnosis of breast cancer? 3.What are the main types of treatment of breast cancer? 4.What is the screening procedure for breast cancer and when should it be started?