Kanker Payudara sebagai

Model Terapi Kanker

AM
EARLY Breast Cancer

Dr Abdul Muthalib
Sub Bagian Hematologi Onkologi
Medik
Bagian Ilmu Penyakit Dalam
FKUI-RSUPNCM-RSKD AM
 BREAST CANCER
Worldwide incidence in females*
Western
Europe 67.4

Eastern
Europe 36.0

Japan 28.6

Australia/
New Zealand 71.7

South Central
Asia 21.2

Northern
Africa 25.0

Southern
Africa 31.5

Central
America 25.5

North
America 86.3
*Incidence per 100,000 population.
AM
Parkin DM, et al. CA Cancer J Clin. 1999;49:33-64.
 BREAST CANCER
Age-specific incidence (per
100,000)
420
400

300
Incidence Rates

United
States
200 England
and Wales
Italy
France
100
Japan

0
20 25 30 35 40 45 50 55 60 65 70 75 80 85+
24 29 34 39 44 49 54 59 64 69 74 79 84

Age

AM
Adapted from New Horizons in Cancer Management, SRI International, 1990.
MASALAH KLINIK KANKER PAYUDARA

Stadium 0 I II III IV

Kasus 12,4 % 41,8 % 33,1 % 8% 4,7 %

Terapi S (HR) S (CHR) SC (HR) SC (HR) CHR

Gol Sembuh Sembuh Sembuh Sembuh Paliatif

5 Yrs
98 % 90 % 70 % 50 % 15 %
Survival

USA 1997 AM
 BREAST CANCER
Cumulative probability of
developing breast cancer
10 In 10 years
9.0 9.1
9 In 20 years
% Developing Breast Cancer

In 30 years
8
7.1 7.1 7.1
7 6.5
6 5.7

5
4.3 4.1
3.9
4 3.6
3 2.4
2.0
2 1.6

1 0.4

0
30 40 50 60 70
Age (years)
AM
Adapted from Feuer EJ, et al, JNCI. 1993.
 BREAST CANCER (Staging
1)
Tumor definitions
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ,
or Pagets disease of the nipple with no tumor
T1 Tumor 2 cm or less in greatest dimension
T1mic Microinvasion more than 0.1 cm or less in greatest dimension
T1a Tumor more than 0.1 cm but not more than 0.5 cm in greatest
dimension
T1b Tumor more than 0.5 cm but not more than 1 cm in greatest
dimension
T1c Tumor more than 1 cm but not more than 2 cm in greatest dimension
T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension
T3 Tumor more than 5 cm in greatest dimension
T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only
as described below
T4a Extension to chest wall
T4b Edema (including peau dorange) or ulceration of the skin of the
breast
or satellite skin nodules confined to the same breast
Used with the permission of the American Joint Committee on Cancer (AJCC AM ), Chicago, Illinois.
T4c Both (T4a and T4b) The original source for this material is the AJCC Cancer Staging Manual, 5th edition (1997)
published by Lippincott-Raven Publishers, Philadelphia, Pennsylvania.
T4d Inflammatory carcinoma
 Staging (2)
kelenjar getah bening : N

N0: tak ada metastasis ke KGB

N1: metastasis pada > 1 ipsilateral
dan moveable
N2: metastasis pada > 1 ipsilateral
dan fixed
N3: metastasis ipsilateral KGB
mammary internal

AM
 Staging (3)
METASTASIS : M
Mo : tak ada metastasis
M1 : metastasis jauh
atau : ke KGB supraclavicular
ipsilateral

AM
 Staging (4)
In situ stage 0 Tis N0 M0
Early invasive stage I T1 N0 M0
stage IIA T0 N1 M0
T1 N1 M0
T2 N0 M0
stage IIB T2 N1 M0
T3 N0 M0
Locally stage IIIA T0 N2 M0
advanced and T1 N2 M0
regionally T2 N2 M0
advanced T3 N1 M0
T3 N2 M0
stage IIIB T4 N (any) M0
T(any) N3 M0
Disseminated stage IV T(any) N (any) M1

AM
 BREAST CANCER (Staging 1)
Tumor definitions (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Tis(DCIS) Ductal Carcinoma in situ
Tis(LCIS) Lobular Carcinoma in situ
Tis(Pagets) Pagets disease of the nipple with no tumor
T1 Tumor 2 cm or less in greatest dimension
T1mic Microinvasion 0.1 cm or less in greatest dimension
T1a Tumor more than 0.1 cm but not more than 0.5 cm in greatest
dimension
T1b Tumor more than 0.5 cm but not more than 1 cm in greatest
dimension
T1c Tumor more than 1 cm but not more than 2 cm in greatest dimension
T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension
T3 Tumor more than 5 cm in greatest dimension
T4 Tumor of any size with direct extension to (a) chest wall or (b) skin, only
as described below
T4a Extension to chest wall,not including pectoralis muscle
T4b Edema (including peau dorange) or ulceration of the skin of the
breast
or satellite skin nodules confined to the same breast
Used with the permission of the American Joint Committee on Cancer (AJCC AM
), Chicago, Illinois.
T4c Both (T4a and T4b) The original source for this material is the AJCC Cancer Staging Manual, 6th edition (2002)
published by Springer-Verlag New York Berlin Heidelberg.
T4d Inflammatory carcinoma
Regional lymph Node (N)
Clinical
NX : Regional lymph nodes cannot be assessed (e.g, previously removed)
N0 : No regional lymph node metastasis
N1 : Metastasis in ipsilateral axillary lymph node(s)
N2 : Metastases in ipsilateral axilarry lymph node fixed or matted, or in clinically
apparent* ipsilateral internal mammary nodes in the absence of clinically
evident
axillary lymph node metastasis
N2a : Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or
to other
structures
N2b : Metastasis only in clinically apparent* ipsilateral internal mammary nodes and
in the
absence of clinically evident axillary lymph node metastasis
N3 : Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary
lymph
node involvement, or in clinically apparent* ipsilateral internal mammary
lymph
node(s) and in the presence of clinically evident axillary lymph node
metastasis ; or
metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary
AM
or AJCC 2002
Pathologic (pN)a
pNX : Regional lymph nodes cannot be assessed (e.g, previously removed, or nor
removed
for phatologic study)
pN0 : No regional lymph node metastasis histologically, no additional examination
for
isolated tumor cell (ITC)

Note : Isolated tumor cell (ITC) are defined as single tumor cells or small cell
clusters not
greater than 0,2 mm, usually detected only by immunohistochemical (IHC) or
molecular methods but which may be verifed on H & E stains. ITCs do not
usually
show evidence of malignant activity e.g, proliferation or stomoral reaction.

pN0(I-) : No regional lymph node metastasis histologically, negative IHC

pN0(I+) : No regional lymph node metastasis histologically, positive IHC, no IHC
cluster
than 0,2 mm
pN0(mol-) : No regional lymph node metastasis histologically, negative molecular
findings
(RT-PCR)b
pN0(mol+) : No regional lymph node metastasis histologically, positive molecularAM
findings AJCC 2002
pN1 : Metastasis in 1 to 3 axillary lymph nodes, and/or in inteernal mammary nodes with
microscopic
diseses detected by sentinel lymph node dissection but not clinically apparent **
pN1mi : Micrometastasis (greater than 0,2 mm, none greater than 2,0 mm)
pN1a : Metastasis in 1 to 3 axillary nodes
pN1b : Metastasis in internal mammary nodes with microscopic disease detected by sentinel
lymph node
dissection but not clinically apparent**
pN1c : Metastasis in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with
microscopic disease detected by sentinel lymph node dissection but not clinically
apparent.**
(Ifassociated with greater than 3 positive axillary lymph nodes, the internal mammary
nodes are
classified as pN3b to reflect increased tumor burden)
pN2 : Metastasis in 4 to 9 axillary lymph nodes, or in clinically apparent* internal mammary
lymph
nodes in the absence of axillary lymph node metastasis
pN2a : Metastasis in 4 to 9 axillary lymph nodes (at last one tumor deposit greater than 2.0 mm)
pN2b : Metastasis in clinically apparent* internal mammary lymph nodes in the absence of
axillary
lymph node metastasis
pN3 : Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in
clinically
apparent* ipsilateral internal mammary lymph nodes in the presence of 1 or more
positive axillary
lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic
metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymphAM
nodes AJCC 2002
Clinically apparent is defined as detected by imaging studies (excluding lymphoscintigraphy)
or by clinical examination

** Not clinically apparent is defined as not detected by imaging studies (excluding

Lymphoscintigraphy) or by clinical examination

AM
AJCC 2002
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis

STAGE GROUPING

Stage 0 Tis N0 M0
Stage I T1* N0 M0
Stage IIA T0 N1 M0
T1* N1 M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
Stage IIIA T0 N2 M0
T1* N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
Stage IIIB T4 N0 M0
T4 N1 M0
T4 N2 M0
Stage IIIC Any T N3 M0
Stage IV Any T Any N M1

*T1 includes T1mic

Note : Stage designation may be change if post surgical imaging studies reveal the presence of distant metastases
provided that the studies are carried out within 4 month of diagnosis in the absence of disease progression AM
and
Provided that the patient has not received neoadjuvant thaerapy
AJCC 2002
Survival rates in breast cancer patients as a function of nodal
status in the axillary and internal mammary lymph nodes
% survival

Both
Author N IM/AX+ IM+/AX Positive
Bucalossi et al., 1971 610 56 79 28

Caceres, 1967 425 52 56 24

Li & Shen, 1983 1242 60 73 38

Urban & Marjani, 1971 500 68 64 54

Veronesi et al., 1983 995 72 88 56

IM: Internal mammary lymph nodes; AX: axillary lymph nodes

AM

AJCC 2002
Five-year survival in 24,740 breast cancer cases
AM
Cancer 63:181-187,1989
1.Low axillary-Level I
2.Mid axillary Level II
3.High axillary,apical-Level III
4.Supraclavicular
5.Internal mammary nodes AM
 Breast Conserving Therapy
BCT : Contra indication
Absolute :
Prior RT to the breast or chest wall
RT during pregnancy
Diffuse suspicious or malignant appearing microcalcifications
Multicentric disease
Positive pathologic margin
Relative :
Multifocal disease requiring or more separate surgical
incisions
Active corrective tissue involving the skin (especially
scleroderma and lupus)
cT > 5 cm (category 2B)
Focally positive margin

AM
 Sentinel node meeting All of the following criteria :
Stage I & II
Unicentric cancer
Tumor cT<5
No large prior excision in upper, outer quadrant (>6 cm)
No prior chemoth/ or hormonal th/
AND
experienced sentinel node TEAM
Team must have documented experience with SN
biopsy in breast center
Team include :
Surgeon
Radiologist
Nuclear medicine physician
Pathologist
Prior discussion with medical and radiation oncologist on use of
SN for treatment decision

AM
INGAT
Clinical Staging : cT.N.M
Pathological Staging : pT.N.M.
Data Patologi lain :
Tumor Grading (Bloom Richardson)
ER +/-
PR +/- Lymphatic
L.V.N. vascular invasion
neural sheet

HER2/Neu
Berapa KG B yg (+) dari minimum 10 buah

artinya perlu : - ahli bedah yg baik (onkologi)

- patologi
AM
 CARCINOMA OF THE BREAST KEY PROGNOSTIC
INFORMATION

Elston Scarff /Bloom/Richardson(SBR) Major Prognostic

Grading System with Elston/Ellis factors:
Modification Axillary nodal status
Gland Nuclear Mitotic Tumor size
count/ Histologic type
Point Formation Pleomorphism 10 HPFs Histologic grade
1 >75% Minimal 5 Age
2 10-75% Moderate 6-10
3 <10% Marked >10
Good prognosis Bad
prognosis
Point Score Grade Tubular
3-5 I Metaplastic
6-7 II Mucinous
8-9 III Medullary
AM
Microinvasive
Ten years Disease Free Survival Estimates with
Locoregional Therapy Alone(i.e. No Systemic
Adjuvant Therapy)

No. of TUMOR SIZE

Positiv
e
nodes
<1 cm 1-2cm 2-3cm 3-4cm 4-5cm >5c
m
0 90 81 75 69 63 56
1-3 60 56 50 47 42 37
4-6 46 42 38 35 31 27
6-9 36 32 29 26 21 AM 13
 NIH
Post-Mastektomie-Bestrahlung
Indikationsstellung:
N> 3+
T 5 cm
T4-Karzinome

AM
 Dt. Konsensus:
XRT nach Mastektomie
Gesichert: Ungesichert:
T3, T4, T2 >3cm Multifokalitt
Multizentrisch EIC
Lymphangiosis, Rezeptor negativ
Hmangiosis Diffuser Mikrokalk
Sicherheitsabstand 1-3 LK+
< 5mm, Pectoralisfaszie Mehrere Biopsien non in
R1, R2 sano
>3 LK + Alter < 35 J

Sauer R, Schulz KD, Hellriegel KP (2001) Strahlenther Onkol AM

177:1-9
 The Adjuvant Therapy Of Primary Breast Cancer

ER + ER
PREMENOPAUSE POSTMENOPAUSE PREMENOPAUSE POSTMENOPAUSE

LOW RISK
ER+,N-,G1,T1a(<1cm)
TAM or None Not Applicable

ANY OTHER Ovarian ablation

(surgery/radiation) TAM Polychemotherapy
(CAF,CEF,AC or
RISK
or Supression adequately dosed CMF)
(GnRH agonists + TAM
at least 2 years)
+/ TAM
Or
or

Polychemotherapy Polychemotherapy
(CAF,CEF,AC or (CAF,CEF,AC or
adequately dosed adequately dosed
CMF) CMF)
+ TAM + TAM

St.Gallen 2000
AM
 Adjuvant therapy of breast cancer risk evaluation
( St.Gallen 2001)

Node Negative Node Positive

Minimal/low risk Average /high risk*

HR And all the And at least one

(+) following: of the following: All High Risk
pT < 2 cm, pT> 2cm,
grade 1, grade 2-3,
age > 35 age < 35

HR And any other factor

(-)

* Lymphatic and/or vascular invasion

AM
Adjuvant treatment for breast cancer treatment guidelines: St. Gallen 2001

Endocrine Endocrine
Non-responsive Responsive
ER and PgR ER and/or PgR
(-) (+)
Node negative Node positive

Minimal/low risk Average/high risk

Chemotherapy Tamoxifen
Nil
OA + Tam Tam CT+ Tam Tam + CT
CT + Tam Tam + CT OA + Tam Tam
OA
PRE POST PRE POST
MENOPAUSAL STATUS
AM
 Adjuvant Chemotherapy
Node (-) : Node (+) :
CMF FAC/CAF
FAC/CAF FEC/CEF
AC AC + Paclitaxel
EC
TAC
ACMF
ECMF
CMF
ACx4 Px4(q 2wks)
(GCSF)
ATC(q 2wks) (GCSF)

AM
 A CMF :
(limited to patient with 4 or more nodes)
AC x 4 Paclitaxel x 4 Better in 5 3 and OS
36 mos
A x 4 T x 4 C x 4

AM
 Comparative ADR and EPI Cardiactoxicity

25

20
% Probability CHF

15

10

250 500 750 1000 1250 1500

0

Cumulative Anthracycline dose in mg/m2

AM
AM
 Hormones affecting the breast
Gonadotrophins Oestrogens
(FSH + LH) Progesterone

Premenopausal
Ovary

Prolactin
Growth hormone

Pituitary gland Corticosteroids

LHRH Pre/post- Adrenal
(hypothalamus) menopausal glands
Androgens Oestrogens

Adrenocorticotrophic
hormone Progesterone
(ACTH)
Peripheral conversion
AM
 Mechanism of action of anti oestrogen
Gonadotrophins Oestrogens
(FSH + LH) Progesterone

Premenopausal
Ovary
goserelin - down-
regulation of LHRH
receptors Prolactin
Growth hormone

Pituitary gland Corticosteroids

LHRH Pre/post- Adrenal
(hypothalamus) menopausal glands
Androgens Oestrogens
Adrenocorticotrophic
hormone Progesterone
(ACTH)
Peripheral conversion
AM
 Stimulatory
Growth Factors PARACRINE

IGF-1
decrease
Cell Replication
IGF-1R X Decrease
(arrest in G1)
AUTOCRINE ERE
DNA
AE

ER
TGF
DECREASE EGFR
TGFR

Inhibitory
Growth Factors
Antiestrogen
AM
APOPTOSIS
 A Adrenal

Extraglandular Cancer cell

Tissue
A A A (370) A
Aromatase
E1 E1(46) E1
Sulfatase
E2 E2(17) E2
E1S
E1 S E1 S
(420)
AM
Plasma Plasma
RESPONSE PENGOBATAN
TAMOXIFEN
ER PR S-phase RR
Fraction
+ + 4,3 74-81%

+ _ 6,3 34-41%

_ + 7,4 33%

_ _ 11,2 10%
AM
De Vita 7th ed.

AM
METASTATIC BREAST CANCER
OPTIMAL ENDOCRINE THERAPY IN
POST MENOPAUSAL WOMEN

1970 1980 1990 2000

TAM 3rd generation

A.I.
TAM 3rd generation TAM/Pure A.E.
A.I.

Megace/ Exemestan/ Megace

Aminogluthetimide
Megace
AM
 Metastatic Breast Ca
Combination vs Sequential single agent
Combination : Docetaxel+Capecitabine
Single :
Doxorubicin
Paclitaxel
Vinorelbin
Capecitabine
Docetaxel
Gemcitabin

AM
 Herceptin
PCH :
Paclitaxel
Carboplatin AUC 6
Herceptin
Single :
Herceptin + Paclitaxel
+ Doce
+ Vino

AM