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Malignant diseases of the breast

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Presentation on theme: "Malignant diseases of the breast"— 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 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 % 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 y, 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 III. Exam. m.- mammography

15 III. Exam. m.- mammography
Evaluation Reccomendation not done repeat 1 negative usual management 2 benign 3 probably benign follow-up every 3-6 m. 4 suspicious biopsy 5 probably malign complex therapy American College of Radiology, 1995

16 III. Exam. m.- mammography
Incidence starting screening in significant reduction of mortality Mortality Zavedení screeningu 110 Mortalita žen ve věku 110 100 100 90 90 80 80 Although the incidence of breast cancer in the UK increased steeply following the introduction of screening in 1988, it levelled off in 1992 at about 25% higher than in 1987 In the UK between 1990 and 1994, mortality from breast cancer (age 55–69) declined steeply. This may have been due to the widespread adoption of tamoxifen, as well as to the introduction of screening in 1988 Mortality from breast cancer in the US also declined between 1989 and 1993, partly as a result of mammographic screening and the consequent increase in early diagnosis of the disease Reference Quinn M, et al. Br Med J 1995; 311: 1950 60 70 80 87 90 94 Rok Quinn M, et al. Br Med J 1995; 311: 4

17 III. Exam. m.- mammography
% pravděpodobnost detekce 100 MG US 80 palpace 60 40 20 5 10 15 20 25 30 35 40 45 50 velikost nádoru v mm

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:

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 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
Histologic type Staging Prognosis Risk factors Kancerogenesis Characteristics of the tumour cell Therapy

34 VI. Invasive breast carcinoma
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell 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
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell 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 2. Staging - metastasis Brain + Skin + Lung + + + Pleura + + +
Liver + + Adrenals + + Bone

40 VI. Invasive breast carcinoma
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell 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
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell Therapy

43 4a. Risk factors Breast cancer development probabilty in next 10 years in the relation with age age risk 20 1 z 2000 30 1 z 256 40 1 z 67 50 1 z 39 60 1 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/ , mortality: 35/

48 4f. Epidemiology

49 VI. Invasive breast carcinoma
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell 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 Menarche lifestyle 1. delivery defekty apoptozy,
antioxydační ochrany, opravy DNA accumultaion of defect DNA INDUCTIONCancerogens Radiation Hormones PROMOTION Hormones Growth factors BRCA carcinoma

52 VI. Invasive breast carcinoma
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell 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
Histologic type Staging Prognosis Risk factors Cancerogenesis Characteristics of the tumour cell 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.
benign normal follow-up Diagnosis of non-palpable l. (MG, US) probably benign check-up in 6 month suspitious larger lesion localisation + biopsy benign (core-cut, FNA) smaller lesion localisation+exstirpation benign + 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 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 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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