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Malignant diseases of the breast Michael G. Halaska Dept. of Obstetrics and Gynecology 2nd Medical Faculty, Charles University.

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Presentation on theme: "Malignant diseases of the breast Michael G. Halaska Dept. of Obstetrics and Gynecology 2nd Medical Faculty, Charles University."— Presentation transcript:

1 Malignant diseases of the breast Michael G. Halaska Dept. of Obstetrics and Gynecology 2nd Medical Faculty, Charles University

2 I. The breast reproducion - nutrition secondary sexual sign - maturition of the women, important role in sexual life S. Freud – the role of the breast in the satisfaction of oral libido

3 II. The structure of the gland 15-20 lobus, which is divided into 20-40 lobulus basic structure of the gland: terminal ductolobular unit (TDLU) - consists of acini and terminal intralobular duct - hormonally sensitive, estrogens - ductus, progesteron, prolaktin - lobus - size 0,3-0,6 mm (10-100/lobulus)

4 II. Structure - TDLU

5 II. Structure - arterial supply rr. perforantes from a. mammaria interna (a. thoracica interna) a. mammaria externa (a. thoracica lateralis) a. thoracoacromialis a. thoracica suprema (a. axillaris)

6 II. Structure - venous supply circulus Luschke circulus Halleri (under the areola)

7 II. Structure- lympahytic supply lateral parts along a. thoracica lateralis into the axilla upper parts to the apical axilla and subclavicular lymph n. internal parts - a. thoracica interna - mediastinal lymph n.

8 III. Examination methods self-examination (2-3 cm) physical exam – aspection, palpation (1-2cm) US- excellent differenciation between solid and cystic structure - complementory to MG,young women with higher density of the gland - pregnant women MRI, CT, SPECT, PET ductography

9 III. Examination methods cytology a) secretory: from the nipple b) punction (FNA) - not by an suspition of malignity - 15-20% false negative benign malign

10 III. Examination methods punctional biopsy – core-cut biopsy open biopsy

11 III. Examination methods c) Mammotome - vacuum assisted - not possible to evaluate the borders d) ABBI - 3D localisation - 20 mm diameter - possible to evaluate the borders

12 III. Exam. m.- mammography over 35 y. detection ability: from 1-3 mm dose 0,1-0,2 rad a) screening: 1. entry 35-40 y, 2. 40-50 y every 2 y., 3. over 50 y every 1 y (- 75 y.) - mortality reduction 20-45% b) diagnostic

13 III. Exam. m.- mammography

14

15 EvaluationReccomendation 0not donerepeat 1negativeusual management 2benignusual management 3probably benignfollow-up every 3-6 m. 4suspiciousbiopsy 5probably maligncomplex therapy American College of Radiology, 1995

16 Incidence starting screening in 1988 - significant reduction of mortality starting screening in 1988 - significant reduction of mortality Quinn M, et al. Br Med J 1995; 311: 1391-1395 Mortality 110 100 90 80 0 110 100 90 80 0 1950607080879094 Rok Zavedení screeningu Mortalita žen ve věku 55-69 III. Exam. m.- mammography

17 05101520253035404550 0 20 40 60 80 100 velikost nádoru v mm % pravděpodobnost detekce MG US palpace III. Exam. m.- mammography

18 IV. Benign diseases A) Non-proliferative: RR < 1,5 fibroadenoma, cysts, metaplasy, fibroadenosis, papiloma B) Proliferative lesion without atypia: RR 2-3 moderete and severe form of ductal hyperplasy C) Proliferative lesion with atypia: RR 4-5 atypic ductal/lobular hyperplasy Dupont,WD.,Page DL.,N Engl J Med,1985, 312:146-151

19 1a. Fibroadenoma round, well circumscribed from lobulus proliferation of epithelial and stromal components hormonally dependent a) pericanalicular b) intracanalicular

20 1b. Fibroadenoma doesn´t increase the risk of breast cancer therapy: - conservative: follow-up every 6 month - radical: surgical extirpation italian study: extirpation leads to RR=2,0 (only follow-up) RR=0,97

21 2. Cysts one of the most common changes from the lobular acini proliferation of the stromal component leads to an increased density of the gland therapy: conservative or punction of the cyst

22 3a. Fibrocystic changes present at 50-90% of women between 35-50 years of age, often asymptomatic dysproportion of the involution - decrease of the amount of the stromal component (dominance of epithelial component) histopathologic finding: fibrosis, cysts, adenosis, lymfoid infiltration, periductal inflammation

23 3b. Fibrocystic changes intensity of mastopatic changes which doesn´t correlate with the intensity of complaints belongs to non-proliferative lesions of the breast zero proliferation indexes lead to worse mammographic lucidity therapy: conservative

24 4a. Papiloma from the main ductus serose or bloody secretion from the nipple therapy: extirpation

25 4b. Juvenile papilomatosis young women (under 20 years) solid, palpable formation (2-3cm) often upper outer quadrant multicystic

26 4c. Multifocal papilomatosis from TDLU combination of epithelial and cystic changes precancerosis therapy: extirpation, dispensarisation

27 5. Cystosarcoma phylloides phyloides tumor proliferation of stromal component histologicaly commemorates intracanalicular fibroadenoma often metaplasy: bone therapy: extirpation, often relaps

28 6. Rare tumours lipoma adenolipoma myoepitelioma desmoidal tumour

29 7. Inflammation juvenile hypertrophy - stromal hyperplasy duktektasis - dilatation of the large ductus in perimenopausis or menopausis mechanical obstruction (deficiency of vit. A) cyklic mastodynie, palp. lesion, inflammation signs therapy: symptomatic, ATB, excision subareolar absces - chronic fistula therapy: incision, drainage, ATB fat necrosis - trauma, radiotherapy, surgery

30 V. Carcinoma in situ A)Ductal carcinoma in situ – DCIS B)Lobular carcinoma in situ – LCIS RR amplified 8-10x

31 A) Ductal carcinoma in situ ductal epithelium has been replaced by carcinoma cells which doesn´t penetrate the basal membrane often recidives in the place of biopsy microcalcifications often present therapy: extirpation + radioterapy or simple mastectomy

32 B) Lobular carcinoma in situ few clinical features no microcalcifications in 15-45% bilateral recidives bilateral LCIS – high risk

33 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Kancerogenesis 6. Characteristics of the tumour cell 7. Therapy

34 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

35 1a. Histologic type ductal carcinoma: 70-80% intraductal c.- type of DCIS lobular carcinoma - 10 % - difficult to detect by mammography (no calcifications) medullar carcinoma - up to 5% - good prognosis, doesn´t involve lymph nodes mucinous - coloid carcinoma - 3% - very slow growth papilar carcinoma - 1% - bloody secretion

36 1b. Histologic type - special ca inflammatory carcinoma – 1-4%, erythema, increased temperature, surgical treatment contraindicated, primary treatment: radiotherapy Paget´s disease (carcinoma) – 4-5%, erosive lesion of the nipple

37 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

38 2. Staging T1 – tumour < 2 cm T2 – tumour 2-5 cm T3 – tumour over 5cm T4 – penetration of the tumour into the chest N1 – isolated metastasis, moveable l. nodes N2 – isolated metastasis, fixated l. nodes N3 – metastasis in internal mammary l. nodes M1 – distant metastasis

39 Brain + Skin + Lung + + + Pleura + + + Liver + + Adrenals + + Bone + + + + 2. Staging - metastasis

40 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

41 3. Prognosis smaller than 1 cm: survival rate 90-95% tumor 2-3 cm: survival rate 65% involvement of 1-3 LN: survival rate 62% involvment of more than 4 LN: survival rate 32% positivity of estrogen/progesterone receptors EGF receptor – worse grade, lymfatic invasion

42 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

43 4a. Risk factors Breast cancer development probabilty in next 10 years in the relation with age agerisk 201 z 2000 301 z 256 401 z 67 501 z 39 601 z 29 Cancer Commitee of the College of American Pathologists, 1998

44 4b. Risk factors sex - frequency of ca female x male: 135 : 1 age - 65 years over 30 years: RR 17 absolute risk in 50 years: 7-10% menarche – early onset: RR 2 first delivery – delivery after 20. year: RR 2-3 menopausis – late menopausis: RR 2 breast feeding over 1 year reduces the risk by 20%

45 4c. Risk factors FH- 1.line: RR 2 - 3 - 2.line: RR do 1,5 genetic carcinoma breast/ovary (BRCA 1,2) - tumour supresor gen, AD heriditary - absolute risk: 85% life style, body weight – alcohol, obesity (BMI > 35), hyperinsulinemie

46 4d. Risk factors environment – chemical cancerogens, genotoxic substances society status: high socioeconomic standart, stress radiation drugs- prolactine agonists HRT - slight elevation by the use over 10 years (kontroversy)

47 4e. Epidemiology incidence: 90/100 000, mortality: 35/100 000

48 4f. Epidemiology

49 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

50 5. Cancerogenesis oncogene activation genetics: genes BRCA 1,2, p53 1. Iniciation: during menarche - first delivery cancerogenes, radiation, nutrition, endogenous hormones 2. Promotion: premenopausis (hormones) postmenopausis - failure of apoptosis, failure of control of the cell cycle

51 5. Cancerogenesis 10 20 30 40 50 carcinoma BRCA 1. delivery lifestyle INDUCTION Cancerogens RadiationHormones Menarche PROMOTIONHormones Growth factors defekty apoptozy, antioxydační ochrany, antioxydační ochrany, opravy DNA opravy DNA accumultaion of defect DNA

52 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

53 6. Characteristics of tumour cell no control of proliferation loss of intercell adhesion loss of epithelium-stromal interaction (loss of contact inhibition of growth) loss of diferenciation elevated metabolic activity changes of HR, abnormal reaction to hormones

54 VI. Invasive breast carcinoma 1. Histologic type 2. Staging 3. Prognosis 4. Risk factors 5. Cancerogenesis 6. Characteristics of the tumour cell 7. Therapy

55 7a. Therapy survival rate is given by the stage radiotherapy reduces the incidency of loco-regional metastasis lymphadenectomy decreases the frequency of local recidives in cases of negative lymph node negativity lymphadenectomy is only staging

56 7b. Therapy - surgery radical mastectomy (Halstead) quadrantectomy segmentectomy tumorectomy/WLE modified radical mastectomy subcutaneous mastectomy plastic operations

57 7c. Therapy - surgery primary surgery: tumors of stage I, II (size < 5 cm) standard therapy: modified radical mastectomy (mastectomy, ALND I, II) lymphatic mapping: sentinel lymph node axillary lymphadenectomy is being still indicated by invasive breast cancer

58 7c. Therapy - SLNM patent blue Tc scintigraphy

59 7d. Therapy - surgery Breast conserving surgery: 1977 - B. Fisher, J.L. Hayward, U.Veronesi condition: - tumour size 3 – 4 cm - tumour is not located in the breast center - tumour is not multifocal - radiotherapy must follow

60 7e. Therapy - plastic operations

61 7f. Therapy - plastic operations

62 7g. Algorithm in non-palpable l. Diagnosis of non-palpable l. (MG, US) benignnormal follow-up probably benigncheck-up in 6 month suspitiouslarger lesion localisation + biopsybenign smaller lesion localisation+exstirpation benign (core-cut, FNA) + peroperative histology malignant operation of malignancy according to surgico-oncological standards

63 7h. Radiotherapy I:T2, over 4 positive LN intensity of radiation: 4-6 MV - linear acc. after conservative surgery - dose of 50 Gy (5 weeks + boost 10-15 Gy – Ir192) radiotherapy of the scar, axilla paliative radiotherapy of metastasis

64 7h. Radiotherapy

65 7i. System therapy - chemot. only systemic therapy can improve prognosis combined chemotherapy - neoadjuvant – before surgery - adjuvant – after the surgery CMF, FAC, AT, ET cyklofosfamid, 5-fluoruracil, metotrexate, doxorubicin, epidoxorubicin

66 7j.System therapy - hormonal t. estrogen receptor blockage - antiestrogens - tamoxifen, raloxifen synthesis blockage - aromatase inhibitor - arimidex high dose progesterones - down regulation of estrogen and progesterone receptors ovarian ablation surgical/radiotherapeutical

67 7k. Prevention proper nutrition and life style: age of the first delivery – breast feeding reduction of environmental risk factors (ionisation radiation, cancerogenes, alcohol) early diagnosis and adequate therapy (system) chemoprevention - antiestrogens: Tamoxifen (USA,UK, Itálie)

68 7k. Phytoestrogens isoflavonids (Genistein): soja, tofu, kari, beer, bourbon flavonoids (Galanin): tea leafs lignands (Indol-3-Carbinol): spinach, broccoli monoterpens (limonen): lemon karotenoids: (lutein, lycopen): tomatoes

69 Edwin Smith - 3000-2500 pnl If thou eaxminest a man having bulging tumors of his breast (and) thou findest that (swelling) have spread over his breast; if thou puttest thy hand upon his breast upon these tumors, (and) thou findest them very cool, there being no fever a all therein when thy hand touches him: they have no granulation, they form no fluid, they do not generate secretion of fluid, and they are bulging to thy hand. There is no ( treatment).

70 Thank You for Your attention


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