Endocrine aspects benign and malignant disorders of the breast

1. Endocrine aspects benign and malignant disorders of the breast Jacek Pytel

2. Epidemiology 50%-70% women „have problems with breasts” during their life

3. Epidemiology • 50% of American women are consulted for breast diseases • 25% are undergoed breast biopsy • 12% are developed some variant of breast cancer

4. Epidemiology • Breastcancer –the most commonsite-specificcancerinwomen • 33% of allfemalecancers • 20% of thecancerrelateddeathsinwommenisresposible of breastcancer

5. Epidemiology • 211300 invasive breast cancers were diagnosed in the USA in 2003 • 39800 (18,9%) died from the cancer

6. Epidemiology • USA • 2009 – 192 570 new cases 40320 (20,9%) died

7. Epidemiology • 13314new breast cancer were diagnosed in 2006 in Poland; 5221(39,2%) died from the breast cancer • 2005 – 13385; 5112 (38,2%) • 2000- 10987; (42,9%)

8. Epidemiology • 2005 – 13385 new cases (44,5/100 000) 5112 died 2000 – 10987 new cases 4712 died

9. Embryology and functional anatomy • In most mammals, paired breasts develop along two ventral bands of thickened ectoderm (mammary ridges, milk lines) at the fifth or sixth week of fetal development • This ridges disappear after short time exept for small portions that may persist in the pectoral region

10. Embryology and functional anatomy of the breast Accessory breasts (polymastia) Accessory nipples (polythelia) may occur along the milk way

11. Embryology and functional anatomy of the breast

12. Embryology and functional anatomy of the breast

13. Embryology and functional anatomy of the breast

14. Embryology and functional anatomy of the breast • The breasts are identical in males and females at birth • Enlargement of the breast at birth may be evident and secretion may be produced in response to maternal hormones that cross the placenta

15. Functional anatomy • In female the breast remains udeveloped until puberty • Ovarian estrogen and progesterone initiate proliferation of the epithelial and connective tissue elements and it enlarges the breast • The breasts remain incompletely develop until pregnancy occurs

16. Functional anatomy • Amastia – absence of the breast is rare • Poland’s syndrom – hypoplasia or complete absence of the breast, costal cartilage and rib defects, hypoplasia of the chest wall and brachysyndactyly

17. Functional anatomy • Iatrogenically breast hypoplasia Induced prior to puberty: trauma, infection, radiation therapy

18. Functional anatomy

19. Functional anatomy • The breast is composed of 15 to 20 lobes • Lobes are composed of several lobules • Each lobe of the breast terminates in a major duct, which opens through constricted orifice into the ampulla of the nipple

20. Functional anatomy

21. Breast anatomy

24. Functional anatomy

25. Functional anatomy

26. Functional anatomy • In the early phase of the menstrual cycle, minor ducts are cord-like with small lumina • At the time of ovulation, with estrogen stimulation, alveolar epithelium increase, in high, duct lumina become more prominent and some secretions accumulate • When the hormonal stimulation decrease, the alveolar epithelium regresses

27. Physiology

28. Physiology

29. Physiology of the breast • Breast development and function are initiated by variety of hormonal stimuli: Estrogen, progesterone, prolactin, oxytocin, thyroid hormone, cortisol, growth hormone

30. Phisiology of the breast • Estrogen initiates ductal development • Progesterone is responsible for differentiation of epithelium and lobular development • Prolactin is the primary hormonal stimulus for lactogenesis in late pregnancy and postpartum period

31. Phisiology of the breast

32. Phisiology of the breast Breast changes associated with menstrual cycle: 1.Increase of DNA synthesis in ductolobular epithelium during luteal phase 2.Increse of cell deletion during the luteal phase. Concomitant vacuolization of the basal layer of the epithelium. 3.Luteal increase in the number of lobules at each ovulatory cycle. 4.Increased cellularity of the stroma and perilobular lymphocytic infiltration during premenstrual phase. 5.Premenstrual phenomenon of engorgement: increase in extracellular fluid, breast size, tension

33. Phisiology of the breast • At the end of the menstrual cycle, there is an increase in size and density of the breast, which is followed by engorgement of the breast tissue and epithelial proliferation. With the onset of menstruation, the breast engorgement subsides and epithelial proliferation decreases

34. Phisiology of the breast Pregnancy – the breast enlarges as ductal and lobular epithelium proliferates First and second trimesters – ducts branch and develop Third trimester – fat droplets accumulate in the alveolar epithelium and colostrum fills the alveolar and ductal spaces Late pregnancy – prolactin stimulates the synthesis of milk fats and proteins

37. Phisiology of the breast Menopause – decrease in secretion of estrogen and progesterone by ovaries – involution of the ducts and alveoli of the breast. The surrounding fibrous connective tissue increases in density and the breast tissues are replaced by adipose tissues

38. Phisiology of the breast

39. Physiology of the breastGynecomastia • Gynecomastia – enlarged breast in the male • Physiologic gynecomastia – occurs in: neonatal period adolescence senescence Common to each of phases: an excess of circulating estrogens in relation to circulating testosterone

40. Physiology of the breastGynecomastia • Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues • Adolescence gynecomastia – an excess of estradiol relative to testosterone • Senescent gynecomastia – circulating testosterone levels falls, resulting in relative hyperestrinism

41. Gynecomastia

42. Gynecomastia

43. Gynecomastia Pathophysiologicmechanisms of gynecomastia I. Estrogen excessstates A. Gonadalorigin 1. Truehermaphroditism 2. Gonadalstromal (nongerminal) neoplasms of thetestis 3. Germcelltumors (chorioncarcinoma, seminoma)

44. Gynecomastia B. Nontesticulartumors 1. adrenalcorticalneoplasms 2. Lung carcinoma 3. Hepatocellular carcinoma

45. Gynecomastia Pathophysiologic mechanisms of gynecomastia: C. Endocrine disorders D. Diseases of the liver-nonalcoholic and alcoholic cirrosis E. Nutrition alteration states II. Androgen deficiency states A. Senescence

46. Gynecomastia B. Hypoandrogen states (hypogonadism) 1. Primary testicular failure (Klinefeltr’s syndrome, eunuchoidal males etc) 2. Secundary testicular failure (trauma, orchitis, cryptorchidism, irradiation C. Renal failure III. Drug – related (cimetidine, ketoconazole, phenytoin, spironolactone, antineo- plastic agents, diazepam, reserpine, theophylline, verapamil, tricyclic antidepressants, furosemid

47. Gynecomastia Treatment: 1.androgen deficiency – testosterone administration may cause-regression 2. medications – then these are discontinued if possible 3. endocrine defects – specific therapy

48. Gynecomastia When gynecomastia is progressive and does not respond to other therapies, surgical therapy is considered Breast cancer in men may also occur

49. Benign breast diseases ANDI - Abberations of Normal Development and Involution - classification of benign breast conditions are: 1. benign breast disorders and diseases related to the normal process of reproductive life and involution

50. Benign breast diseases 2. there is a spectrum of breast conditions ranges from normal to disorder to disease 3. the ANDI classification encompasses all aspects of the breast condition, including pathogenesis and the degree of abnormality