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Vol 8, No 2, April - June 1999 Histopathological aspects

of

breast cancer 133

Histopathological

aspects

of breast

cancer

in

relation to

some

epidemiological

risk

factors

Esti

Soetrisno*, Gunawan

Tjahjadi*, Goi Sakamoto',

Joedo

Prihartonot, Yoshiyuki Ohnof,

Didid Tjindarbumi#,

Santoso

Cornain*,

Setyawati

Budiningsiht,

Sadao

Suzuki4

Muchlis

Ramli#,

Idral

Darwis#, Endang

Sri Roostini*,

Kenji Wakai[

Drupadi

S

Dillon.

Abstrak

Penelitian epidemiologik dengan cara kasus kontrol pacla 300 kasus kanker payudara di Rumah Sakit

Dr

Cipto Mangunkusumo,

telah clilakukan pada tahun 1989-1991. Dengan menggunakan klasifikasi yang dianjurkan oleh Japanese Breast Cancer Society,

gam-baran histopatologik kanker payuclara menunjukkan bahwa dari tipe karsinoma duktus invasif,

jenis

skirus ditemukan pada 147 kasus

(49VoI jenis padat tubuler pada 79 kasus (26.33Vo) danjenis papiLotubuler pada 39 kasus (t3Vo). Sednng dengan menggrmakan

klasi-fikasi WHO ( 1981 ), ditemukan 265 kasus (88.337o) invasif duktus karsinoma, karsinoma invasif lobuler pada 7 kasus (2.337o), karsinoma moduler pada 17 kasus (5.68Vo), karsinoma adenoid kistik pada

I

kasus (0.33Vo), penyakit Paget pada puting 2 kasus (0.67Vo) dan 4

kasus pada karsinoma noninvasif adalah karsinoma duktal insitu. Analisa terhadap faktor-faktor risiko yang bermakna pada kanker

payudara wanita Indonesia menuniukkrtn bahwa faktor-faktor: aktivitas seksuaL dini, tinggal

di

daerah perkotaan, traluna payudara, obesitas (kegemukan), haid pertama,/menarche yang terlambat, siklus haid yang tidak teratut; menopause, konsumsi makanan berlemak dan yang mengandung santan dapat meningkatkan risiko. Juga telah dianalisa hubungan antara faktor-faktor risiko yang bermakna tersebut dengan jenis histopatologik. Hasilnya menunjukkan bahwa Konsumsi makanan bersantan meningkatkan kemungkinan jenis karsinoma duktus invasif. Pengaruh tersebut berhubungan dengan ketiga subtipe histologik, yaitu papiler tubule4 solid tubuler clan

skirus. Konsumsi minuman clengan santan/air kelapa dan sayuran segar menurunkan kemungkinan jenis tersebut, dengan sifat tklak bergantung kepada subtipe histoLo gik.

Abstract

Case control epidemiological study of 300 breast cancer casès from

Dr

Cipto Mangunkusumo HospitaL has been performed in 1989-1991. By applying the Japanese Breast Cancer Society classification, the histopathological pafiern ofbreast cancer showed that from the invasive ductal carcinoma type, scirrhous type was found

in

147 cases (49Vo), solid-tubular type

in

79 cases (26.33Vo) and papilotubular type in 39 cases (I3Vo). According to WHO classification (1951); they were diagnosed as: invasive ductal carcinoma in 265 cases (88.33Vo), invasive lobular carcinoma in 7 cases (2.33Vo), medullary carcinoma in

I7

cases (5.68Eo), adenoid cystic carcinoma

inI

case(0.33Vo),purePaget'sdiseaseof thenipplein2cases(0.67Vo)and4cases(l.33Eo)of thenoninvasivecarcinomawereductal carcinoma in situ. Analysis of the signfficant riskfactors among the Indonesian female breast cancer revealed that the following factors:

living at urban area, young sexual activity, trauma, obesity, late menarche, irregular cycle, menopause, fafiy diet and coconut milk

con-taining food consu'mptiolx increased the risk. Relationship of the riskfactors to histopathological types has been stastistically analyzed. The resubs showed that increased possibility to have the invasive ductal carcinoma was related to consumption of coconut milk containing food. The effect was relatecl to the three histological subtypes, namely: papillary tubuLar, solid tubular arul scirrhous types. Coconut milk drinks andfreshvegetables showed decreasing effect, whichwas irrespective to subtypes.

Keywords: Breast cance4 histopathological, epielemiological, riskfactors.

* Department

of Anatomic Pathology, FacuLty of Medicine, University of Indonesia, Jakarta 10430, Indonesia

' Department of Pathology, Cancer Institute Hospital,

Tbkyo 170, Japan

t

Department of Community Meclicine, Faculty of Meclicine, University of Indonesia, Jakarta 10320, Indonesia

ll Department of Preventive Meclicine, Nagoya University

School of Medicine, Nagoya 466, Japan

# Department of Surgery, Faculty of Metticine,

University of Indonesia, Jakarta 10430, Indonesia

I

Department of Nutrition, Faculty of Medicine,

University of Indonesia, Jakarta 10430, Indonesia

INTRODUCTION

(2)

134

Soetrisno et al

Paget's disease

of

the nipple.

In

1986,

the

Japanese

Breast Cancer Society

suggested

to

observe

more

carefully on the

most

common invasive

breast

carci

noma:

IDC. As

the result

of

their

study,

there

are 3

IDC

which were easily identified by

ic

examination, namely:

Papilotubu-bular IDC,

and

Scirrhous

IDC.

These

3

subtypes

of

IDC

have

l0

years survival rate

of

77 .4Vo, 64.9Vo and

6I.ZVo respectively.a

Age influences on

some breast cancer types

in

rela-tion

to

prognostic

decision. For example:

lobular

car-ular

c

disease,

usually

elder

ma

on

reproduc-in

wo

der

age

in

men,

Junevile secretory carcinoma

on

childhood,

muci-nous

carcinoma among the 5th

decade,

medullary

car-cinoma

in

the

lower

decade.

In

general,

it

was

known

that

some breast cancer

types have a specific

biologic

behavior: indolent, circumscribe

or

aggressive,

dif-fuse/massive

invasive.5-12

Some

difference

on

histological type might

be

found

among

different

races.

In

comparative study between

Japanese

and

American female

breast cancer,

it

was

revealed

that

lobular carcinoma

among

Japanese

fe-males

was

significantly

lower

than

that

among

American

females.

The

Japanese

breast cancer cases

had

better

survival

compared to

the

American

cases.5

ogical

ighest

carci-noma

was

reported more

frequently

among

the

black.

In this

paper,

we

present the analysis on the

relation-ship between

certain histological

types

of

breast

can-cer

to

certain demographic characteristics and risk

factors.

MATERIALS

AND METHODS

Co

nicopathology

of

s (rqsq_rqgO)

usi

matched

con-Based on

Tjahjadi

et

al.l3

and

S

al.t4 data,

it will

be studied whether

histo

I

types

of

breast cancer

showed

any

to

some

epidemiological

data.

The result

of

case

distribution

Med

J Indones

by

histological types was as

follows:

noninvasive

ductal carcinoma (DCIS)

4

cases

(l.33Vo), invasive

ductal

carcinoma

(IDC)

265

cases

(88.3

ing

of

3

subtypes

papilotubular

IDC

39

solid-tubular

IDC 79

cases

(26.33Vo),

s

I47

cases (49Vo),

mucinous

carcinodra

6

cases

17 cases

(5.68Vo),

in-7 cases (2.33Vo), ade-33Vo)

andPaget's

dis-vo).

The distribution

according

to tumor location

showed

that tumors were

mostly

located

at

the

left

breast

I72

cases

(57.33Vo),

followed by

right

breast

lI7

(39Eo)

and

11 cases (3.67Vo)

were

bilateral.

The

epidemiological

study on the 300

cases

of

breast

cancer revealed several

significant risk factors, listed

as urbaner,

young

first

sexual

contact, trauma,

obe-sity, late

menarche,

irregular cycle,

coconut

milk

food, no

vegetable,

and as significant

at

lVo

meno-types,

3

tubular,

to

inva-ation to

certain

risk

factors. Thus,

living

area,

menopausal

of

coconut

food

tables

were

st the

sive

ductal

com_

pared

to

other types.

They

were

further

evaluated

against

the three histological

subtypes.

The

propor-tions were

compared

by chi-square calculatiôn with

correction

for

continuity.l6

16r,

for

trend was

per-formed using loglinear

regression

model

with

pàis-son error.15

RESULTS

Basic results

of

our

300

cases

breast cancer

study

presented

in

the

following

tables.

ive

the

ma

of

ductal type (DCIS):

l.33Vo, paget,s

disease

of

the

(3)

Vol 8, No 2,

April

- June 1999

Table

1.

Histological types and case distribution of breast

can-cer (1989-1991)

Histological types Number of

cases

%

2.

t. Noninvasive carcinoma

-

Ductal

-

Lobular Invasive carcinoma

a.

Invasive ductal carcinoma

a.1. Papilotubular

a.2. Solid-tubular

a.3. Scirrhous

b.

Special type

b.

l.

Mucinous

b.2. Medullary

b.3. Invasive lobular

b.4. Adenoid cystic

Pagets disease

4 0

39 79 l4'1

6

17 7

I

2

1.33 0.00

r 3.00 26.33

49.00

1.33

5.68 z-J.t 0.33

0.67

Total 300 100.00

Source: Tjahjacli et aL. 1993

Tâble

2.

Case distribution by age at operation/biopsy

Age at operation/biopsy Number of cases E

HistopathoLogical aspects

of breast cancer

t3s

o

@

years Figure 1. Histogram offrequency tlistribution by age of group

of

300 cases of breast cancar

(IDC)

type was analyzed

in

relation

to living

area,

menopausal status, consumption

of

coconut

milk

containing

food

and drinks,

fatty

meat

and

fresh

vegetables.

The results are given

in

Table 3.

There

was

no

significant

or

difference

in

relation

to

IDC

type

or

IDC

type comparing between

rural

and

urban

area,

with

x2

=

0.009.

Similarly,

if

they were

com-pared according

to

menopausal status,

with

x2

-0.400.

Consumption

of

coconut

milk

food

seemed

to

in-crease

the possibility

to

have invasive

ductal

carci-noma compared

to

other types.

Significant difference

was

shown

by women who

consumed

coconut

milk

food

less

than once a week,

with

x2

=

5.885,

p

<

0.02.

Somewhat

similar pattern was shown

by

consump-tion of

coconut

milk

drinks, except

for

significantly

decreasing

effect

related

to frequent consumption

(3-4

times

weekly), with

x2

=

4.731,

p <

0.05.

Consum-ing fresh

vegetables

daily

showed to

decrease the

risk

significantly. Further

analysis

was

performed

by

evaluating the three

subtypes

of IDC,

namely

papil-lary

tubular type,

solid

tubular

type

and

scirrhous

type.

The results

are

given in

Table

4.

Accordingly,

there was

no significant

difference

among three

histological

subtypes

in

relation

to

liv-ing

area.

However, there

was

marginal significance in

oro)ooroooo,

AFN(fJ$n@1.-oooooooc!s)<t(n@t.

20 - 29 years

30 - 39 years

40 - 49 years

50 - 59 years

60 - 69 years

70 - 79 years

t3

'72

93

55

58

9

4.33

24.00

31.00

18.33

19.33

3.00

Total 100.00

The

peak incidence was

found

in

the

5th

decade:

3lVo.

The

youngest

case

reported was

2i

years old,

and

the oldest

case was

75

years

old.

The young

peo-ple

group

(less

than

30

years

old)

showed

much

lower

percentage

in

comparison

to

the older

people

group (more than 40

years

old),

they were

4.33Vo

ver-sts

77.66Vo.

The

mucinous carcinoma

which

were

only

4

cases

(1.337o)

occurring

at

30

years,

44

years,

51 years and 54

years

old respectively. The lobular

and

medullary

types

were similarly distributed in

the age

interval

over 20

to

70

years.

Among our

11

bilat-eral

breast cancer

cases,

only

2

cases

of

them

were

lobular

type.

The possibility

of

any

kind

of

relationship

between

the

histopathological

types

of

the 300 cases

of

breast

cancer and significant

risk

factors was

etnalyzed

by

cross tabulation.

The

invasive

ductal

carcinoma

300

[image:3.595.325.567.90.341.2]
(4)

136

Soetrisno et aL

relation

to

menopausal status.

Somewhat

increasing

effect

was related

to

solid

tubular

type

with

x2

=

3.786,

p

between 0.25-0.05.

Increased

possibility

to

have

papillary

subtype was shown

in

women

con-suming coconut

milk

containing food

less

than

once

a

week

with

x2

=

6.685,

p<0.01.

Such an

effect

was

also shown

by

the other

subtypes,

namely:

solid

tu-Table 3.

Med

J

Intlones

bular type

with

x2

=

4.014,

p<0.05

and scirrhous

type

with

x2

=

4.857

, p<0.05.

The

tests

for trend

were

not

significant at

p

level

of

0.05.

No

significant

differ-ence was seen

for

coconut

milk drinks, fatty

meat and

fresh

vegetables

consumption

relative

to

respective

histological

subtypes.

Risk factors Invasive Ductal Carcinoma Others Total x2

1. Living area Rural Urban

Test tbr trend: 2.

2. Menopausal status No

Yes

Test for trend:

3. Diet of coconut

milk

containing food Never

Less than

lx

weekly

l-2

weekly 3-4 weekly Daily

Test tbr trend:

4. Diet of coconut

milk drink

Never

Less than

lx

weekly

l-2

weekly 3-4 weekly Daily

Test for trend:

5. Diet of

fatty

meat Never

Less than

Ix

weekly

l-2

weekly 3-4 weekly Daily

Test for trend:

6. Diet of fresh vegetable Never

Less than

lx

weekly

1-2 weekly 3-4 Daily Daily

Test for trend:

93

172

0.001,

P = NS

1r8

147

0.02,

p = NS

6l

92 57 39

l8

0.007,

P = NS

r59

80

l5

t0

I

0.08,

p = NS

79 80 67 JJ

6

0.007,

P = NS

53 42

46

57 67

0.48,

p = NS

5.885+

< O.O2

t382

1.052

0.33 t

0.400

3.212

0.000

4.73t*

< 0.05

0.204

t.809

0.569 0.106

2.320

0.599 0.002

2.619

4.915*

< 0.05 12

23

105 195

r35

165

0 009

t7

l8

t2

6 7 5 J

25 6 3 6

1

73 98 64

44

21

t84

86

l8

ll

1

63 48 56 62 71 7

15

l0

J

0

l0

6

l0

5

4

86 95 77 36

6

[image:4.595.84.582.174.739.2]
(5)

VoL B, No 2, ApriL

-

June 1999

Thbel

4. Analysis of risk factors

and histological type of 300 breast cancer cases

HistopathologicaL aspects

of

breast cancer

Histological type

Risk f'actors Papillary

tubular IDC

Solid tub.

IDC

Scirrhous IDC

x2 Others Total

1.

)

3.

Living

area Rural Urban

Menopausal status No

Yes

Diet of coconut

milk

containing food Never

Less than lx weekly

1-2 weekly 3-4 weekly Daily

Test

for

trend: Diet of coconut

milk drink

Never

Less than lx weekly

l-2 weekly

3-4 weekly Daily

Tbst

for

trend:

Diet of

fatty

meat Never

Less than lx week'ly

1-2 weekly 3-4 weekly Daily

Test

for

trend:

Diet of fresh vegetable Never

Less than lx weekly

1-2 weekJy

3-4 weekly Daily

Tbst

for

trentl:

19 20 23 56 2',1 52 52 95 '72 75 6.685+* 4.593* r.610 0.652 0.222 4.014* 0.729 0.280 0.301 1.341 4.857+

0.8 t9

1.379

r.863

0.612

12

105

23

195

135 16s

l2

6 7 5 3 0.642 0.217 0.617 0.308 2.297 0.001 1.813 0.846 0.130 0.469 3.421 0.273

0 077 0.1 05 1.321 2.022 0.101 3.786 3.368 0.068 2.136 0.085 0.091 o.201 3.625 0.03 8

2.929 0.004 0.708 0.675 0.238 0.290 2.536 0.4r6 2.475 0.021 1.502 3.291 2.383 184 86 18 11 1 6 t4

l2

5 2

2l

28 t7 10 -) 34 48 28 24 13 t5 98 64 44

2t

4. 28 9 1 I 0

il

lt

t0 6 1 9 5 9 8 8 85 46 9 6 I 25 6 J 6 I 7 15

l0

3 0

l0

6 r0 5 4 46 25 5 J 0 5. 29 21 20 8

I

39 48 3t 19 4 86 95 77 36 6 3.207 1.004 0.0r 8

3.182 t.437 6. r8 t4 l3 l5 t9 39 48 37 34 40 63 48 56 62

7I

0.525 0.077 1.222 3.1 48 0.142

'k

Significant

dffirence

at p<0.05;

"{'

Significant

dffirence

at p<0.01

DISCUSSION

The

age

distribution of the

Indonesian

female

breast

cancer showed

that

a

significant

increase

of

the

pro-portion of cases

has

started

at

the

third

decade (2480) and

peaked

at the

fourth

decade (37Vo).

The

data

sug-gested

that the

breast cancer

in

Indonesian

females

started at younger

ages

compared

to

the American

and

the

Japanese cases.s-13

The proportion

sharply

declined at the

seventh decade,

similar

to the

Japa-nese cases

but

differs

from

the

American cases,

which declined

at

the eighth

decade.

The

histological typing

showed that the

majority

was
(6)

I

38

Soetrisno et al

invasive ductal carcinoma

and 9.67Vo

special

type.

Thus,

only a few

non-invasive carcinoma

(l.33%o)

and Paget's disease

of

the nipple

(0.67Vo).

The

pro-portion

were different

from

the

Japanesg ç4sss,5-13

with

higher non-invasive

cases (1.4Vo),

lower

inva-sive ductal carcinoma (80.4Vo),lower special

types

(1I.4Eo) and

similar

Paget's

disease (0.7Vo).

The

pre-sent

study

has

analyzed the

relationship

between

sev-eral

significant risk

factors

and the

histological

types.

The data

showed

that consumption

of

coconut

milk

containing

food

increased

the possibility

to

have

in-vasive ductal carcinoma

as

compared

to other

histo-logical types,

while

coconut

milk

containing drinks

and

fresh vegetables

had

decreasing effect.

It

is

of

in-terest

that the

increasing

effect

of

coconut

milk

con-taining

food

related

to papillary tubular type

and

the

decreasing

effect

of

coconut

milk

containing drinks

was related

to

scirrhous type.

It

appeared

that

the

for-mer effect was evident

in

all

three histological

sub-types.

The

decreasing

effect

of

fresh

vegetables

was

not preferentially

related

to

any

histological

subtype.

Such

relationship

might

be value

for

better

under-standing

on

the

role

of risk

factors

in influencing

the

development

of

breast cancer.

The

relationship

of

his-tological

types

of

gastric cancer

to

demographic

data

has

been also analyzed

by

others.lT

Further study on

bigger

samples

is

suggested

to

en-able

the analysis on other histological

types and

the

evaluation on important epidemiological risk

factors

such

as

ethnic

difference.

Acknowledgments

The authors would

like to

thank

to

the

nurses, Ms.

Ros and

Emi,

and

public

health

nurses,

Ms. July

and

Ms.

Erlaini for

excellent

epidemiological

data

collec-tion. We are

also indebted

to EDP

staffs

for

helping

in

data processing.

This work was

supported

by

the

Ministry of

Education, Science, Sports

and

Culture

of

Japanese

Govemment,

Grants

No.

0 I

M2007,

MM20

13

andO6042006;

and was

partially

supported

by

the

In-donesian

Cancer Foundation. This

collaborative

study was

a

part

of

Special

Cancer Research

project

in

Monbusho

International Scientific

Research

Pro-gram,

with

the

approval

of

the

Dean,

Faculty

of

Medicine

University of

Indonesia,

No.

43831PTO2.

H4.FK/E/88.

Med

J

Indones

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Table 3.Risk factorsInvasive Ductal Carcinoma

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