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