Breast cancer presentation slides for learning

breast cancer, diagnosis of breast cancer , aetiology of breast cancer, pathophysiologyy of breast cancers, drugs for the treatment of breast cancers, counselling points for breast cancers and education , surgical inyerventions in breast cancer, types of surgical intervention , chemotherapy in breast cancers,

1. Breast cancer Afra A. Y. A gyapong 1

2. OUTLINE I ntroduction Epidemiology Causes/risk factors Pathophysiology Clinical Presentation Management C onclusion 2

3. INTRODUCTION Breast cancer is the most frequently diagnosed life threatening cancer in women, worldwide. It arises from the tissues of the breast usually the ducts and lobules If diagnosed early, it is curable. 3

4. Anatomy of the breast Breast is the tissue overlying the pectoral muscles Specialized tissues that produce milk The amount of fat determines the size of the breast Milk producing part of the breast is organized into 15-20 sections called lobes Within each lobe, there are smaller structures called lobules, where milk is produced. Connective tissue and ligaments provide support to the breast and give it its shape 4

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6. Epidemiology Occurs in both men and women One in eight women are expected to develop the disease over the course of their lifetime. Incidence rates have declined from 1994 due to decreased use of hormone replacement therapy 6

7. Risk factors Gender: Female> Male Personal history of breast cancer Family history of breast cancer Early menarche (<12yrs) Late menopause (>55yrs) Late first pregnancy (>30yrs) Long term use of hormone replacement therapy (estrogen) Inherited gene BRCA 1 and BRCA 2 Oral contraceptives??? 7

8. Pathophysiology Cancers arise through a series of molecular alterations at the cell level Discrete breast tumor subtypes with distinct etiopathogenesis and clinical behavior Exact number of subtypes and molecular alterations are not known but involve the presence or absence of estrogen and progesterone receptors human epidermal growth factor 2 receptors 8

9. BREAST TUMOR SUBTYPES 9 Cancer subtype Hormonal receptor HER-2 receptor Distinct characteristics Luminal A ER and/or PR positive HER-2 negative Low grade, tend to grow slowly, has the best prognosis Luminal B ER and/or PR positive HER-2 negative Grow faster than Luminal A because of high levels of protein ki-67 Triple negative Breast cancer ER and PR negative HER-2 negative Grows and spreads fast. Common in younger women and people with BRCA1 gene mutation HER-2 positive ER and PR negative HER-2 positive Grow faster than luminal cancers. Usually has the worst prognosis but targeted treatment has helped.

10. Types of breast cancer according to % occurrence Invasive Invasive ductal carcinoma: most common type Invasive lobular carcinoma Non invasive Ductal carcinoma in situ Lobular carcinoma in situ Inflammatory breast cancer 10

11. Diagnosis Patient history Physical examination Imaging (Mammogram & Ultrasound) Biopsy 11

12. Clinical Presentation Identification of painless lump in the breast Nipple discharge or retraction Skin changes in the breast ( peau d’orange ?) Metastatic disease (10% pf patients ) 12

13. STAGING OF BREAST CANCER Done to evaluate the extent of the disease and determine best treatment course Stage I- small tumors (< 2cm) with no lymph node involvement Stage II- small tumors with lymph node involvement or larger tumors (>2cm and < 5 cm) Stage III- Larger tumors (>5cm) with lymph node involvement Stage IV-Metastasized to other organs . 13

14. Prognostic factors Larger tumor size Presence of disease in lymph nodes Estrogen and progesterone receptor negative tumors HER-2 positive tumors 14

15. Management Surgery: lumpectomy, mastectomy Radiotherapy Neoadjuvant therapy and Adjuvant therapy Hormonal therapy : SERM, LHRH agonists, aromatase inhibitors, anti-estrogens Chemotherapy: Doxorubicin, Docetaxel, cyclophosphamide, fluorouracil Targeted therapy: Trastuzumab , Neratinib , Pertuzumab 15

16. Management (Chemotherapy) 16 DRUGS MOA DOSAGE SIDE EFFECTS Doroxucibin Anthracyclines: inhibits topoisomerase II function 45-60mg/m 2 IV 3 wks Not to exceed cumulative dose of 450-500 mg/m 2 Cardiotoxicity due to formation of oxygen free radicals, alopecia, leukopenia Paclitaxel Taxanes : Binds to beta subunit of microtubules, inhibit mitosis 80mg/m2/ wks IV Nausea vomiting, myelosuppression, neuropathy, hypersensitivity Cyclophasphamide Inhibits DNA synthesis by forming cross links with DNA 600mg/m 2 IV Leukopenia, alopecia, vomiting, myelosuppression Fluorouracil Activates p53 tumor suppressor gene 500-600mg/m 2 day Neutropenia, alopecia,

17. Management(Targeted therapy) Given to target HER-2 positive breast cancers 17 Medication MOA Dosage Side effects Trastuzumab Monoclonal antibody 5.4mg/ kg IV 3 wks Fever, neutropenia Pertuzumab Monoclonal antibody 840 mg IV loading dose, then 420 mg 3wks Fever, allergic reaction, Neratinib (Cancer growth blocker) Block signaling process cancers use to divide 240mg PO daily for a year UTIs, Nose bleed diarrhea

18. Management (hormonal therapy) DRUG dosage Side effects MOA LHRH agonists Leuprolide Goserelin 7.5mg IM depot 28days 30mg IM 4 mths 3.6mg SC depot 28 days, 10.8 mg SC 3mths Bone mineral density depletion Used in pre-menopause Inhibit pituitary release of LH and FSH Aromatase inhibitors Anastrozole Letrozole Exemestane 1mg PO daily 2.5mg PO daily 25mg PO daily Alopecia, decreased appetite, diarrhea, hot flash, joint disorders Used only in post-menopause. Inhibit enzyme aromatase SERM Tamoxifen Raloxifen 20mg PO daily 5 yrs 60mg PO daily 5 yrs Hot flashes, vaginal discharge, embolism Vasodilation, leg cramps Used in both pre & post menopause. Blocks estrogen from binding to receptor. Anti-estrogen drug Fulvestrant 500mg IM on days 1,15, 29 and once mthly thereafter Nausea vomiting, hot flashes, bone pain Binds to estrogen receptor and targets it for destruction. 18

19. Prevention Prophylactic Mastectomy SERM: Tamoxifen and raloxifene Raloxifen is considered as effective as tamoxifen in prevention with less toxicity such as thromboembolic events and uterine cancer 19

20. References Koda Kimble, Mary A and Loyd Y (2012).Applied therapeutics: the clinical use of drugs. 10 th edition. Baltimore Md. Lippincott Williams & Wilkin pp. Page 2201-2209 Pathak M., Dwivedi S. N., (2018). Neoadjuvant chemotherapy regimens in treatment of breast cancer: a systematic review and network meta-analysis protocol. Syst Rev. 2018; 7: 89. doi : 10.1186/s13643-018-0754-1 Early Breast Cancer Trialists ’ Collaborative Group (EBCTCG ). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet . 2005;365:1687 Kuchenbaecker K. B et al. (2017) Risks of breast, ovarian and contralateral breast cancer for BRCA 1 andBRCA2 mutation carriers. JAMA 2017; 317(23): 2402-2416. The British National Formulary (2020), 80 th Edition, the pharmaceutical Press. London-UK. Pages 946, 1005, 939 20

21. American Society of Clinical Oncology (2020). Selection ofOptimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideliine Update. J Clin Oncol 38. ascopubs.org/journal/ jco . Doi : https://doi.org/10.1200/JCO.20.02510 21

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