Clinicopathological aspects of breast cancer: A joint study between Indonesia and Japan

Clinicopathological

Aspects of Breast

Cancer

:

A

joint

study between Indonesia and Japan

Didid

Tiindarbumi',

Muchlis

Ramli'.

Susumu

Watanabeï.

Idral

Darwis-.

Goi

Sakamoto$.

"

'

iuna*an

Tjahjadi+, Esti Soetrisno+,

Yoihiyuki

Ot"ol,l,'Endang Sri Roosiinit,

Santoso

Cornain+'

.G

Joedo Prihartonor,

Sadao Suzu"t<ill, Setyawati

Budiningsihr, Éenji Wakail

I

Abstrak

Masalah penatalalcsanaan klinik dari kanker payudara tetap penting d.alam hal diagnosis dan pengobatan. Telah d.isarankan oleh penelitian-penelitian terdahulu bahwa perlu d,ipikirkan dua subset kanker payudara, yaitu penyakit yang agresif dan yang

pertumbuhan-nya tidak nyata secara klinis (indolen). OIeh karena itu, penelitian aspek klinikopatologik kanker payudara berkaitan dengan _fenomena sémacam

itu menjadi penting untuk dilakukan pada wanita Indonesia

juga.

Bersamaan dengan penelitian epid,emiologik secara kasus-kontrol 300 kasus kanker payudara telah dianalisa terhadap aspek klinikopatologiknya. Semua kasus dievaluasi secara klinis menggunakan klasifikasi intemasional TNM dan Manchester yanç baku dan secara histopatologik menggunakan modifikasi klasifikasi WHO seperti yang dianjurkan oleh Perhimpunan Kanker Payudara

Jepang. Protokol penatalaksanaan kanker

payudara dari Perhimpunan Ahli Bedah Onkologi Indonesia yang d.isesuaikan dengan pedoman yang diterima secara luas diterapkan seperlunya. Hasilnya menunjukkan bahwa kasus-knsus kanker payudara paling sering ditemukan pada golongan umur dibawah 35 tahun dan di anlara 40 dan 44 tahun. Sebagian besar (87 7o) pada stadium lanjut (stadium IIIA, IIIB dan IV) sedangkan hanya

1j

Vo pada stadium

dini(stadiumldanll).

Diantara300kasushanyall0

lasusyangoperabel. Prosedurbedahyangditerapkanadalahsebagaiberikut: mastektomi radilul pada 50 kasus (16.6 Vù, mastektomi sederhana pada 40 kasus (13.37 Vù dan bed.ah konsewasi payudara pada 2 kasus (0.67 Vo). Kejangkitan kelenjar getah bening ditemukan pada 20 dari 50 kasus dengan mastektomi radikal, dan jumlah rata-rata kelenjar getah bening yang didiseksi adalah 6.8. Sebagian besar (88.33 Vo) adalah karsinoma duhal invasif dan sisanya jenis khusus (9.67 Vù dan karsinoma non-invasif (1.j

j

%). Dua kasus (0.67 %) adalah penyakit Paget payudara. Di antara karsinoma duktal invasif jenis skirus merupakan jenis yang paling sering (49 Vo).

Abstracts

Theproblemofclinicalmanagementofbreastcancerremainsimportantinrespecttobothdiagnosisandtreatment. Ithasbeensuggested. from earlier studies that two subsets of breast cancer might be considered, namely the agressive disease and the indolent one. Therefore,

the study of clincicopathological aspects of breast cancer in respect to such phenomena became important to be conducted in Indonesian females as well.

In

parallell

to

the epidemiological case-control study, 300 breasl cancer cases have been analyzed

for

their clinicopathological aspects. All cases were evaluated clinically using standard International TNM and Manchester Classification and hi*opathologically using mod.ified WHO classification as recommended by the Japanese Breast Cancer Society. Breast cancer management protocols of the Indonesian Surgical Oncology Association as adapted _from the widely accepted standards were applied accordingly. The results showed that the breast cancer cases were mostly _{found in} the age group und,er 35 years and. between 40 to 44 years. The majority (87 %) were in advanced stage (stage IIIA, IIIB and

N)

while only 73 Vo were in early stage (stage I,

il)"

Out of 300 cases only 770 cases were operable. The surgical procedures which were applied were as _follows: radical mastectomy on 50 cases (16.6 Vo), simple mastectomy on 40 cases (13.37 Vù and breast conserving surgery on 2 cases (0.67 Vo). Lymph node involvement was found in 20 oul 50 cases with radical masteclomy, and the average number of dissected lymph nodes were 6.8. The majority (88.33 Eù was of invasive ductal carcinoma and the resl were special types (9.67 Vù and non-invasive carcinoma (1.33 Vù. Two cases (0.67 Vù were Paget's disease of the breast. Among the invasive ductal carcinoma the scirrhous îype was the most common type (49 %).

Keywords

:

b reast ca ncer, clinicopathological aspects, surgical p rocedures

Departntent of Surgery, Ftculty of Medicine, Universily of Indonesia Dr. Cipto Mangunkusmo National Central General Hospital,

Jakar-àonæia-

Clinical

management of breast cancer remains

as an

i

x-s.*8try,.cancerlnstitute,Tokvo170,

Po':-.

important

problems,

including its biology,

diagnosis

r

_{of Anatomic Pathologv' Faculry or}

Medi

_rc'

universitv

;;â

1;",

tment.

It

has been estimated

that mortality

s

ll

_{Medicine, Nagoya University,} ,",Totqo170,Ja School

an

of

amounted

breaSt

cançer mOrtality has been obServed in

to

40 7o.l

Considerable increase of the

₂₈

Medicine,

r

_{'' l)epartme}

^

developed

countries

from 1960

to

1980,

with

22

7o

drcutz, Untversrty ol lndone tarJal(arla , '2

..I0i30,Indonæia.

change.'

The prognosis

has been considered poor,

" R<ls"orrh Center

_{for Meilical} Science and Technology, Faculty

of

with

about 5O

%

S-year

relative survival

and

a

15-20

Vol 4, No 3, July - September 1995

an

and

women

3.9

per , breast

cancer rânked the second

i.e. in the

19g9

the relative

It

is

of

interest

to

study the

similarity

and

the dis_

similarity

of

the breast cancer problems between

_the

Indonesian patients and the

Japanese

patients

in

a

collaborative study.

This

study was conducted

to

evaluate the

clinico_

pathological

aspects

of

breast cancer

in

ldonesian

females

in relation

to the

epidemiological

_{study on risk}

factors

in

breast cancer.

The findings

will

response

to

therapy.

status

background w

METHODS

most

instances.

In

all cases

histopathological

examination was

_done

and

for

clinical

al TNM

_{Clas_}

sifications'e

was

and2).

_Based

on the extent of

t

_{metastasis the} cases

were

also

evaluated whether

they

were

operable

or non-operable.

Clinicopathologlt of Breast

Cancer

L4g

radiotherapy

as

adjuvant therapy, according to

_Breast Cancer Management

protocol

_{of the}

Indonesian

_{Surgi_}

cal Oncology Association

(see

Table 1

_).

ffitJr".'fr:fJ

was

adapted

from widely

accepted

pro-RESULTS

The

age

distribution

of

the

300 female breast

cancer are

given

in

Table

1.

The highest

proportion of

_breast

cancer

_cases

were

in

the age group under 35 years and

between 40_44years.

Lower

peak was seen in the age

group

of 60_65

years.

Table 1. Age distribution of 300 female breast cancer

Age in years _No.

ofcases

Vo

<35 35

-39

40-44

45-49

50-54

55-59

60-65

7O+

t7.o

11.3

t7.o 14.0 9.6 8.6 15.3 4.O 3.0 51

34 51 42 29 26 46

I2

9 [image:2.595.311.545.306.454.2]

T able 2. Clinical staging

The Manchester UICC Classification

Stage No. of cases Vo

4

4

No

Mo

Nr"

Mo Tr"

Tru

10.3 Vo

3l

6 4 t2 ,)

'l

No

Mo

No

Mo

Nr"

Mo

Nr"

Mo

Nru

Mo

TN Tzt Tz. Tza '12"

23.6 Vo

71 33 32 3 1 J

)

No

Mo

NI"

MO

Nru

Mo

No

Mo

Nru

Mo

N:

Mo

Tt"

Tl.

Te" Tq" Tq. Ta^

43 Vo

t29

)

t4 4 J 1 11 t3 2'7

l6

27 1

)

3 5

Ttu

No

Mo

Tl

Nt"

Mo

T*

Nt

Mo

T:r

Nz

Mo

T:u

Nr

Mo

Tau Nt

Mo

T.lr

No

Mo

Tlu

Nr"

Mo

Tlu

Nru

Mo

Tau Nz

Mo

T+

No

Mo

Tu

Nt"

Mo

Tl"

Ntt

Mo

Tn.

Nz

Mo

IIIB 61

)

3 3 a J t7 6 3 1r 11 4 4 2 IV

Ttt

Trr Tru Tu Tu Tu Tlu Tat Ta. Ta' Ta. Tru Ta. Nr, Nru Nz Nt" Nru Nt" Nru Nru Nz Nu Nz Nr Nz Mr Mr Mr Mr Mt Mt Mr Mr Mr Mr Mr Mr Mr

203 Vo

Total

Among 50

cases

with

radical

mastectomy,

20

cases showed

lymphnodes involvement

with

positive

metas-tasis and 30

cases showed lymphnodes involvement

with

negative

metastasis. See

also Table

4.

Average

number

of

dissected

lymphnodes

were

6.8

lymphnodes.

Table 4. Numberof Radical Mastectomy cases

with

involve-ment of tbe regional lympbnodes

No. of total

radical

No. lymph

nodes

No. lymph nodes mastectomy

câses involvement

involvement

positivemetastasis negativemetâstasis

[image:3.595.71.568.61.812.2]

Vol 4, No 3, July - September 1995

The

operable cases

were evaluated for their tumor

site

and

the

results can be

seen

in

Table

5. patients

with

radical mastectomy was higher than the one with

simple

mastectomy

(16.6 %

and

13.37

%

of

the

total

300 breast cancer

cases

respectively. BCT

was

only

performed on

2 cases.

Table 3. Number of patients o[ respective surgical method

Surgical method No. of operable cases Peroentage

(from all 300)

Clinicopathologt of Breast

Cancer

151

Table 6. Distribution of 300 breast canær qrses _{according to}

histological types

Histological types _Number

of

_Vo

casqs

Non invasive carcinoma: a. Non invasive ductal

carcinoma

b. Lobular carcinoma in situ

1.33

Invasive carcinoma

a. Invasive ducîal carcinoma:

a7

papillotubular

a2

solid tubular

a3

scinbous

39 79 r47 13.00 26.33 49.00 Radical mastectomy

Simple mastectomy

Lumpectomy / BCT

50 40 2 L6.6 13.37 0.67

b. Special types:

bt

mucinous carcinoma

bz

medullary carcinoma

br

invasive lobular

carci-noma

b+

adenoid

cysticcarci-noma

Total

Most of

breast cancers

were

found in

the

upper outer

quadrant

(73.9

Vo),

followed by

upper inner

quadrant

(I0.8

%o),lower

inner

quadrant (8.6

%),subareolar

(4.3 7o) and

lower

outer quadrant

(Z.l

Eo).

Table

5.

Distribution ofoperable breast cancer cases

accord-ing tumor site

Site

No. of cases Percentage

The

histological typing

was evaluated

on

110 operable cases, as can be seen in Table 7.

Similarly,

the

invasive

ductal carcinoma

were

dominant, consisting of

mostly

(64.54

7o) the

scirrhous type,

followedby

12.72 To

of

papillo{ubular type

and

7.27

%

of solid-tubular

type.

The

rest

were the special

type

(mucinous, medullary,

lobular

and

adenoid cystic).

Paget's dlsease _o.67

Table

7.

Distribution of 110 operable cases ofbreast cancer

according to histological types

Histological types _{Number of}

cases 92 4

I7

7 1 1.33 5.68 2.33 0.33

Upper outer quadrant

Lower outer quadrant

Upper inner quadrant

Lower i nner quadrant

Subareolar % 68 2 10 8 4 72 2 6 5 1 2 73.9 2.r 10.5 8.6 4.3

Invasive ducfal papillo-tubular carcinoma

Invasive ductal solid tubular carcinoma

Invasive ductal scinhous carcinoma

Mucinous carcinoma Medullary carcinoma Invasive lobular carcinoma Adenoid cystic carcinoma

Paget's disease

I4 14.72 7.27 64.54 1.81 5.45 4.54 0.90 1.81

Total 92 ₁₀₀

The results

of histological typing oil all

300 cases are

given in

Table 6. The

majority

tù/ere

the invasive

car-cinoma, consisting mostly (88.33

Vo)

of

the

invasive

ductal

carcinoma

and

9.66 7o

of

the

special type, and

the rest (1.33 7o)were

non-invasive

anrcinoma.

paget's

[image:4.595.322.559.107.392.2] [image:4.595.58.296.332.646.2] [image:4.595.319.555.390.735.2]

DISCUSSION

The

study on

the

age

distribution

of all

breast cancer

patients indicated that the

breast cancer has

already

occured

in

younger

age,

namely under

40

years,

with

relatively

high

proportion. Similar

findings

were seen

in

Jakartars and

in

other

geographicat

area

of

our

country

w it h ra the_r- di

fferent

demo graphica

I

co mpo si

-tion

i.e. East

Java.ro

Such age

distribution

pattern was

similar

to

that

of

Japanese

women but

differs

corsid-erably

from

other

populations such as American

women.4

The

analysis

of

the

stage

of

the

disease has revealed that the

majority

(87

Vo)

were in

advanced stage (stage

IIIA,

IIIB

and

IV)

while only

13 7o were

in early

stage

(stage

I

and

II).

The

present

findings

were

consistent

with

our

previous

data.^'''' This

was

in

contrast to the

pattern

of

breast ca4cer

in

Japan, the

majority

of

cases

were

in

early

stage.)

Out

of

300 breast cancer

patients

only

110 cases were

operable. The proportion

of

cases

that

need radical

rnastectomy was

slightly

higher than

the

simple

mas-tectomy

cases. Our previous study

showed

similar

data

even

after

1O-year

survival observation.lT

Lu--pectomy or

breast

conserving tumorectomy

were

only

performed

in

2 cases

(0.67

7o).

The evaluation on tumor site

showed that

the tumor

occurred

mostly

(73.9

Eo)

in

the upper outer quadrant.

Histological typing

on

all

300 breast cancer cases has

revealed that the

majority

were the invasive carcinoma,

with

predominance

of

invasive ductal type

and

small

proportion

of

special type, while

only

1.33

7o

were

non-invasive carcinoma.

Evaluation

on

110 operable cases

resulted

in

similar findings, i.e. mostly the

in-vasive ductal carcinoma,

two-third of which

were

the

scirrhous

type.

The

latter

has been observed

to show

lower

10-year

survival

rate

as

compared

to

the other

types i.e. papillo-tubular

and

medullary tubular

car-cinoma.)

Paget's

disease

were

only

found

in

2 cases.

Our

data

showed

both sirnilarity

and

dissimilarity

be-tween

the breast

cancer

in

Indonesian women

and the

Japanese

*o-"o.18

Our prelirninary study

of

hor-monal receptor expression

in

50

lndonesian

breast cancer cases

indicated

thatT2o/o were estrogen

receptor

(ER)

rich

breast cancers.

More

than

two-third of

patients

with

moderate differentiation showed

ER-positivity.

Furthermore,

it

contributed

to the evidence

of subsets

of

breast

callcer relative

to its

biological

behavior,

i.e. agressive,

indolent or in between.

Fur-ther study

needs

elucidating

related factors

in

respect

1o such

difference

in biological

behavior.

Thus,

we

anticipated

that clinicopathological

study

would

take the

benefit of

related studies such

as

hor-monal receptors

(estrogen and

progesteron

receptors)

and oncogenes

(c-erbB-2

and

p53).

It

has

been reported

recently

that the expression

of

such

molecular

markers

might

influence

the

risk of

tumor

growt-h, the

disease

prognosis

and the response

to

lherapy.19-22

Acknowledgments

The authors are

grateful

to the nursesMs.

Emi

and

Ms.

Ros

and

for public health

nurses,

Ms. July

and Ms.

Erlaini

for

excellent care and

collection

of

data of

breast cancer cases and

controls.

We

are also

indebted

to

the

laboratory

lechnician for

excellent

work

on the

surgicopathological

specimens.

This work

was supported

by

the

Ministry

of Education

and

Culture,

Japan,

Grants

No.

01042007

and

04042013; and was

partly

supported

by

the

Indonesian

Cancer

Foundation. This collaborative study was

a

part

of

Special

Cancer Research

Project

in

Monbusho

International

Scientific

Research

Program,

with

the

approval of

the Dean,

Faculty of

Medicine, University

of

Indonesia, No. 4383

lPT02.H4.RK /

E

/

88.

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a

aL

Appendix-1

Breast canær management protocol - Indonesian Surgical Oncology Association, December 1989

MedJ

Indones

Stage

I

Tt"

Tru

No-t" No-ta

Mo Mo

Radical mastectony or modified radical mastectomy

If

lymph node negative: observation only

If

lymph node positive: regional imadiation + adjuvant chemotherapy

Stage

II

To

T1" Tru

Tzt

Tu

Tzu

Nru Nru

Nrr

No-1.

Nr

Nru

Mo Mo Mo Mo Mo Mo

Radical mastectomy or modified radical mastectomy with irradiation on

tumor bed and regional lymph node

Stage

III

Any Tr with any N Mo

Any Ta with any N Ms

Any T with N2 Mo

Any

Twith

Ng Mo

Stage

III

is divided into Stage

IIII

and Stage

III3

Stage

IIIA

T3"-4"

No-z

Mo

Tu-zt Nz

Mo

Simple mastectomy with irradiation of tumor bed + regional lymph-node

+ chemotherapy as adjuvant therapy

Stage

IIIB

f36a5-a. any N Mo Considered as non-operable primary treatment is irradiation on

tumor bed + lymphnode region + chemotherapy + hormonal therapy

Stage

IV

Any T any N witb

Ml

Primary treatment is hormonal tberapy. This is divided into 3 groups.

l.Premenopausal women

-

castration / anti estrogen therapy

2.Women with 1-5 yr post menopausal status were evaluated for the estrogen activity on vaginal smear:

If positive

.-

castration/or anti estrogen tberapy

If

negative

-

considered as post menopausal case

+

anti estrogen therapy

3 Women after5 yrs post menopausal status

-

estrogen therapy

Estrogen and Progesteron receptor assessmeDt in respect to the therapy is not yet done routinely in our Hospital

Notes:

Adjuvant chemotherapy is given with the regimen of CMF (6 cycles).

C

_{=Cyclophosphamide orally 60-80 mgm2lday,day} 1 until day 14.

M =Methotrexate 4O mglm2 i.v., day 1 and day 8.

F

=5 Fluorouracil 600/m2 i.v., day 1 and 8.

I

Vol 4, No

j,

July - Septenber 1995

Appendix-2

Breast Cancer Classification:

TNM

system (UICC) Tumor size (T)

Clinicopatlnloglt of Breast

Cancer

155

Not palpable

=2m

_{>2-5 cm}

>5cm

No deep fixation To Tr

Tu

T:.

With

[ixation

Tru

_Tza

Any size + direct chest extension Any size + skin infiltration or oedema

or peau d'orange or satelite nodule confided to same breast

Tau

T+

T+t

T++Tnu+=T4c

Nodal Status (N)

No

Nr

Nrr

Nz

Homolateral axillary nodes Not palpable Palpable Palpable Palpable

Clinical non-malignant

Clinical

malignant Malignantfixed

Homolateral clavicular node(s) clinically malignant or oedema of arm

Nr

Metastases (M)

Mo

No clinically apparent distant metastases

Mr

Distant metastases apparent

The Manchester / UICC Classification

Stage I

Tt"

Tz.

NoNo Mo

Stage

Il

To

Tt"

Tz^

Nr

Nr Nr

Mo

Stage

III

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