Breast Cancer Statistics

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2 Breast Cancer Statistics Incidence Mortality Prevalence 2

3 Breast Cancer Incidence

4 Breast Cancer Mortality

5 Breast Cancer Prevalence ~$100,000

6 Female Breast Anatomy Breasts consist mainly of fatty tissue There is also epithelium lobes ducts 6

7 Mammary epithelium

8 Where does breast cancer originate? Ductal Carcinoma Lobular Carcinoma

9 In situ vs Invasive 9

10 Where does breast cancer Metastasize? 10-15% 50-70% 15-20% 40-50% 10

11 Breast cancer classification: why? 11

12 Breast cancer classification: classic factors

13 Breast cancer classification: Tumorrelated factors (prognosis) 13

14 Breast cancer classification: Tumorrelated factors (prognosis)

15 Breast cancer classification: Tumorrelated factors (predictive-hr) 15

16 Breast cancer classification: Tumorrelated factors (predictive-her2) HER2-(~80%) HER2+(~20%) HR+(50%) HR-(50%)

17 Breast cancer classification: Tumorrelated factors (predictive-tnt) Non TNT(~80%) TNT(~20%) -Heterogeneous group EGFR P53mut PTEN deletion Myc amp JAK2 amp

18 Breast cancer MOLECULAR classification 18

19 Breast cancer MOLECULAR classification 19

20 Breast cancer MOLECULAR classification: Luminal A 20

21 Breast cancer MOLECULAR classification: Luminal B 21

22 Breast cancer MOLECULAR classification: HER2+ 22

23 Breast cancer MOLECULAR classification: Basal 23

24 Inherited predisposition to breast cancer -5-10% of all breast cancers are hereditary -Two autosomal dominant genes, BRCA1 and BRCA2 account for almost all cases of familiar breast cancers (60-80% probability to develop BC.) -Dozens of other genes with less penetrance and more uncommon. -Cancer syndromes from mutations in: TP53 (Li-Fraumeni syndrome) ATM (Ataxia Telangiectasia) STK11/LKB1(Peutz-Jeghers syndrome) PTEN (Cowden syndrome)

25 Inherited predisposition to breast cancer: BRCA genes BRCA1 and BRCA2: Involved in DSB repair by homolog recombination.

26 Breast cancer: Risk factors

27 Breast cancer: Risk factors

28 Breast cancer: Treatments overview Local control -Neo adjuvant Chemotherapy -Surgery -Radiation therapy Systemic control -Chemotherapy -Hormone therapy -Targeted therapy

29 Breast cancer treatments: Neoadjuvant chemotherapy Definition: Administration of therapeutic agents before a main treatment. Goal: Aims to reduce the size or extent of the cancer before using radical treatment intervention, thus making procedures easier. Standard: Anthracycline-taxane based regimens.

30 Breast cancer treatments: Surgery Goal: Removal primary tumor mass. Standard: -Lumpectomy: designed to remove a discrete lump. -Mastectomy: designed to remove the entire mammary gland.

31 Breast cancer treatments: Radiation Definition: Administration of high-energy radiation to damage the DNA of cancer cells. Goal: Destroy cancer cells located in a given area Standard: -External-beam radiation therapy (most common). -Brachytherapy.

32 Breast cancer treatments: Adjuvant chemotherapy Definition: Administration of therapeutic agents after a main treatment. Goal: Destroy cancer cells remaining at any location in the body. Standard: Anthracycline-taxane based regimens.

33 Breast cancer treatments: Adjuvant Hormone therapy Definition: This kind of treatment is helpful only for HR+ breast cancers. Stop estrogen from acting on breast cancer cells or lower estrogen levels. Goal: Destroy/inhibit the growth of cancer cells that depend on continuous action of steroid hormones. Standard: -Tamoxifen: Blocks estrogen receptors in breast cancer cells. -Aromatase inhibitors (AIs): Drugs that stop estrogen production.

34 Breast cancer treatments: Adjuvant Targeted therapy Definition: Rational design of therapeutic approaches based on the specific characteristics of the patient and/or patient s disease to optimize the clinical benefits. Goal: Destroy/inhibit the growth of cancer cells that depend on specific aberrant functions (specific/efficient). Standard for HER2+

35 Breast cancer treatments: Multidisciplinary team approach Scientist 35