A case-control study of breast cancer among Japanese women in Tokyo

Vol 4, No 3, July - September 1995 Breast Cancer Among Japanesse Women 177

A

Case-Control Study of Breast Cancer among

Japanese

\ilomen

in Tokyo

Kenji

Wakai', Yoshiyuki

ohno', Sadao

Suzuki*,

Susurnu WatanabeT,

Goi Sakamotot

and

Nakako

Kubo$

Abstrak

Untuk meneliti _faktor risika kanker _{payudara saat ini, dilakukan penelitian kasus-lantrol pada runah-sakit di Tolcyo, dari tahun 1990} sampai 1991. Informasi mengenai _{faktor risiko potensial didapat dari kwesioneryang diisi sendiri} oleh 5.084 pasien rawat jalan.

Dari

pasien tersebut diilapat

i00

kasus kanker payudara, dan dipilih 900 kontrol secara acak yang umurnya sesuai. Temuan bermalon adalah: (a) semakin tinggi jumlah kelahiran hidup, semakin kecil risiko pad.a wanita pramenopause (risiko relatif (RR) yang itisesuaikan untuk 3 atau lebih kelahiran hidup terhadap tanpa kelahiran hidup: 0,24; 95Vo interval kepercayaan (IK) : 0,08 - 0,65); (b) pada wanita Pramenopause, siklus haid teratur meningkatkan risiko (RR yang disesuaikan: 2,50; 95Vo IK : 1,16-5,35), dan peningkatan lama siklus mengurangi risiko (P untuk kecenderungan linier < 0,05); (c) perokok masa kini mengalami peningkalan risiko

(1,6j;

1,11-2,

j9)

untuk semua wanila, dan

(2,7j;

1,38-5,39) untuk wanita pasca menopause); (d) wanila yang kegemukan mengalami

risiko

lebih besar mendapat kanker payudara pasca menopause: RR yang disesuaikan untuk yang berbobot 70 kg atau lebih terhadap yang berbant 50 kg atau kurang adalah 4,82 (95Vo

IK:

1,53-15,2); (e) semakin tua usia melahirkan anak pertama, semakin tinggi risiko kanker payudara pasca menopause (2,85; 1,16-6,99, dan 3,54; 1,03-12,2 untuk umur 30-34 dan 35 tahun atau lebih). Risiko kanker payudara pra menopause dan pascamenopause ridak berhubungan dengan riwayat kanker payudara pada keluarga, riwayat penyakit payudara jinalg umur saat haid pertama dan menopause, Ialaasi, kebiasaan mkum alkohol dan linggi badan.

Abstract

To explore the risk _factors

for

recent _{female breasl cancer,} a _{hospital-based case-conlrol study was conducted in Tokyo,}

from

_{1990 ro} 1991. Information on potential risk _factors was obtained by a _{self-administered questionnaire from 5.084 out-patients. Of the patients,}

300 incident breast cancer cases were recruited, and 900 age-matched _{controls were randomly selected. Significant}

findingi

_{are: (a)} the more the number of livebirths, the smaller the risk in premenopausal women (adjusted relative .a,sk (RR) _for

j

_{or more binhs relative}

to none: 0.24; 95Vo confidence intental (CI): 0.08-0.65); (b) in premenopausal women, regular menstrual cycle increased the risk (adjusted RR: 2.50, 95Vo CI: 1.16-5.38), and its increasing duration decreased the risk (P

for

_{linear trend <0.05); (c) current smokers}

experienced an increased risk (1.6j, 1.11-2.39 _{for allwomen and (2.73; 1.38-5.j9) for postmenopausalwomen; (d) obesewomenwere} al a Sreater risk of postmenopausal breast cancer: adjusted. RR

for

those weighingT0 kg or more relative to those weighing 50 kg or

Iess being 4.82 (95Vo

CI:

1.53-15.2); (e) the later the age at _{first livebirth, the higher} the postmenopausal breast

,onr"riitk

g2-.BS;

1.16-6.5q and

j.54;

1.03-12.2

for

ages of j0-34 and 35 years and more, respectively). Neither premenopausal nor postmenopausal breasl cancer risk was independently associated with _{family history} of breast cancer, history of benign breast disease, iges at meiarche and menopause, lactatiory drinking habits and body height.

Keywords

Z breast cancer, risk _{factor, premenopausal, postmenopausal}

Risk

factors

incriminated for

female

breast cancer

in-clude

farnily

history

of

breast

caucer,l-8

history of

benign breast

disearç,t'''o early

menaréhe,l'5,0-tz'tur" rnenàpause,2-4'10'l

l'13'

lale

aze at first

birth/full-lenn

pr"grlun.y,

l'3-6'8'e'12't4' t5 unJ

lo*

pa ri ty (a s rna I I num

-ber

of

full-term

pregnancies).1,6,8,e'10'14

Obesity

is also an established

risk

factor for

lreast

cancer among postmenopausal women .l'8,11,16,17

Breast-feeding is reported as a

protective factor

against

breast cancer.

Alcohol

consumotionz'3's'6.8.12'13'18.19 and

smoking

habits3'8'1e-22

,"-"in to

be

explbred

fur-ther as

significant risk

factors

of

breast cancer.

In Japan,

age-adjusted

incidence

(adjusted

by World

Population)

of breast

cancer

was 13.5

per

100,000

population

in

1.g7523

andZ4.3in19B5.2a

this

increase is

conceivably

ascribable to

rapidly changing

lifestyles

among

Japanese women.

It

is, therefore,

of

impor-Departme,tt of Præentive Medicine, School of Medicine, Nagoya

_University,

t_Departmen

_{lrclitnte Hospital, Tokyo 170, Jopan}

+

Departmen

_{rcer lrctilule Hospitat,}

Tolqo

170, Jaoan

ç _D)portmenr

of

_{Pubtic Health, Med.ical School, Nagoyo City}

tance and

significance

to

explore

the recent

risk factors

for

breast cancer among Japanese

women.

METHODS

Inforrnation on potential risk factors

was

obtained by

a

self-administered questionnaire from all out-patients

who visited

the

Department of

Breast

Surgery,

Cancer

Institute,

Tokyo from May 10,

1990 to

May

31,199I.

Items surveyed

were age, menopausal staius,

family

history

of

breast caneer,

history of benign

breast

dis-easç,

regutarity

and duration

of

menstrual

cycle (for

premenopausal

women),

ages

at

menarche

and

rnenopâuse, age

at first birth,

number

of

livebirths,

episodes

of

lactation, smoking and drinking

habits,

height

and

weight.

These

information

have been

readi-ly

collected

from all out-patients before examination,

that

iq

prior

to diagnosis.

Of the

5,084 female patients during

the

study period,

314

were newly

diagnosed

as having

breast

cancer

histologically. Of

the 314

breast cancer

patients,

we

excluded 11 patients

with

missing information

on rnenopausal status, one

patient

under 25 years

old,

and

2

patients

with

history

of

other malignant

tumors.

Tbus, 300 incident

patients

were eligible

cases

for

the present

study.

Controls were randomly selected from

the rernaining

4,770 patients without

breast cancer,

excluding

those

with missing

information

on menopausal status

and/or

with history of

other

malignant tumors.

Three

controls

per case

were randomly

selected,

rnatching

each

other

for

age (as nearest as

possible). Table

I

shows the age

distribution of the study subjects (300

cases

and

900

controls),

and those related

to

the menopausal status.

Table

l.

Age Distributions

o[

Cases and C.ontrols in general and classified by menopausal status

All

analyses

were performed for premenopausal

and

postmenopausal

women,

separately

and totally.

Obesity index was calculated as Quetelet's index,

defined

as

weight (in kilogram) divided by

the second

power of height

(in

meter).

Unconditional multiple logistic regression

analysis2s

was undertaken

to

obtain RRs adjusted

for

age

and

other variables

potentially confounded. In the

multi-variate

analysis,

study subjects with missing

informa-tion were also included

as an

additional category.

A

linear trend

in RRs, derived from the

logi-s-tic

model,

was

examined by

the

method of

Rothman.zÔ

RESULTS

Table

2

shows

the RRs obtained

by

unconditional

multiple logistic

regression analyses.

After

adjusting

for

other variables

(see footnote

of

Table2),

a

significantly

increased

risk ofbreast

cancer

was apparent

among premenopausal

women,

when

menstrual

cycle

was

regular (RR: 2.50;

957o

Cl:

l.16-5.38). The longer

the

duration

of menstrual

cycle,

the smaller the risk

with statistical significance

(P for

trend

<0.05).

Late

age

at first birth

was linked

to

the risk

in

postmenopausal women (2.85; l.L6-6.99)

and

(3.54;

I.03-12.2)

for

age

of 30-34

years,

and

that

of

35 years and

older

respectively. Number of livebirths

was

in-versely correlated

to

breast cancer

risk

in

premenopausal

women

and

all

women, independently

of other factors (P

for trend

< 0.001 and

<0.05,

respec-tively).

All

women Premenopausal Postmenopausal

Ag.

Cases

C)tntrols

Cases

Controls

Cases Controls

20-29 30-39 40-49 50-59 60-69 70-79

80-2.O

8.3 43.7

27.O

t3.3 4.7

1.0

2.O

8.3

43.7

27.O

13.3 5.1 0.6

3.5 14.7

70.0 I1.8 0.0 0.0 0.0

3.5 t4.7 72.7

9.1

0.0 0.0 0.0

0.0 0.0 9.2

46.9

30.8

10.8

2.3

0.2

1.0 9.9

47.8 28.8

LI.I

1.2

l7

7t 352

44 0

0 0 6

25

119

20

0 0

0

18

75

393 243 120

46

5

6 25

t3l

8l

40

t4

-5

0

0

t2

61

40

t4

3

1 4

4I

199

t2a

46 5 [image:2.595.56.531.538.723.2]

Vol 4, No 3, July - September Ig95

Table

2.

Adjusted Relarive Risks

for

Breasr cancer

in

Uncondirionar

Breast Cancer Among Japanesse

Women

179

I-ogistic Regression Analysis'

All

women Premenopausal _{Posmeoopausal}

RR 95%Ct RR 95%Ct RR 95%Cl

Family history of b,reast cancer

lto yes

Past hislory

of

benign breasa disease no

yes Age at nrenarche

-12 t3 t4

15-test for trend Age at menopause

-44 4549 50-54 55-test for trend

Regularity of menstrual cycte

irregu lar regular

Duration of menstrual cycle(days) -27

28-29 30-3r

?7_

tesl for lrend Age at first livebirtb

-24 25-29 30-34

35-test for lrend Number of livebirths

0

1 2

3-tesl for trend Lactation

no-yes

Smoking never smoked ex-smoker currenl snoker Alcobol drinking

no yes(current) Height(cm) -149 150-154 155-159

160-test for arend

Weiglrt(kg) -49 50-59 ffi-69

70-test for trend

1.00

Reference

1.29

0.70

-

2.39

1.00

Reference

0.98

0.65

-

1.46

1.00

Reference

1.09

0.72

-

1.63

o.82

0.s4

-

1.26

0.94

0.63

-

1.42

NS

1.00

Reference

t.u

0.70

-

3.83

1.00

Reference

1.05

0.63

-

1.78

1.00

Reference

t-22

0.74

-

2.Ot

o.79

0.46

-

136

0.93

0.53

-

1.65

NS

Reference

o.2t

-

132 0.17

-

0.95 0.08

-

0.65 P<).001

Reference 0.59

-

2.50

1.00

Reference

0.96

0.42

-

2.20

1.23

0.75

-

2.03

1.00

Reference

1.36

0.92

_

2.W

1.00

Refereoce

0.77

0.37

-

1.62

0.71

0.34

-

L.49

1.08

0.4e

-

2.37 NS 1.00 1.77 1.59 2.76 Reference

t.t2 -

2.8A

0.82

-

3.05 0.96

-

7.89 P< 0.05

1.00

Reference

o.92

0.?l

-

2-67

1.00

Reference

o.73

0.35

-

154

1.00

.Rèference

0.90

0.,10

-

2.05

o.74

0.32

-

t.1l

0.85

0.&

-

t.n

NS

l.m

Reference

0.65

0.29

-

1.45

0.63

0.30

-

1.36

o.Tt

o.25

-

2.37

NS

1.00

Reference

r.û3

0.67

-

158

l.Q

O.Ez

-

2.94

2.17

0.91

-

5.20 NS

1.00

Reference

0.85

0.44

- t.u

0.78

0.43

-

1.44

0:61

0.31

-

1.20

P<0.05

1.00

Reference

1.08

0.65

-

r.80

1.00

Reference

0.91

0.49

-

1.70

t.63 t.tl -

2.39

1.00

Reference

r.u

o.77

-

1.39

1.00

Reference

1.22

0.78

-

1.92

1.13

0.70

-

1.82

1.46

0.86

-

2.48 NS

l.m

Reference

250

1.16

-

538

1.00

Reference

0.80

0.47

-

134

0.66

0.y

-

128

0.50

0.10

-

258 P< 0.05

1.00

Reference

O.ca

0.51

-

1.69

0.q

0.41

-

2.17

1.08

0.28

-

4.18 NS

l.m

Reference

t-25

0.63

-

2A9

2.85

1.16

-

6.ee

3.54

LA3

-

12.2

NS

1.00

Reference

1.68

0.57

-

4.98

1.74

0.62

-

4.88

1.62

0.55

-

4:t4 NS

1.00

Reference

1.00

0.45

-

2.20

1.00

Reference

0.80

0.28

-

232

2.73

1.38

-

539

1.00

Reference

0.71

o.42

-

t.tg

1.00

Reference

1.81

0.98

-

334

1.51

0.76

-

2.98

1.46

0.62

-

3.46 NS

1.00

Refereoce

o.n

o.47

-

1.26

1.09

0.54

-

2.21

4.82

1.53

-

15.2

NS r.00 o-52 0.,m 0.24 1.00 t.2t 1.00 1.18 1.32 3.ffi Reference 0.86

-

1.62

0.84

-

2.08 1.47

-

6.37 NS

'

All wonren: adjusted for age, menopausal slatus and other variables listed. [image:3.595.51.546.96.731.2]

Current

srnokers were at

significantly

greater

risk

in

all

women

(1.63;

l.ll-2.39)

and

in

post-menopausal

wornen

(2.73;

1.38-5.39).

Women, when

weighing 70 kg or

more, were also

at

greater

risk (RR:

3.06

in all

women,

2.76

i.n

premenopausal

women,

ancl

4.82

in

postmenopausal

women).

For

premenopausal

women, a significant

trend

of

increasing risk

with

increasing

weight

was detected

(P

for

trend <0.05).

Farnily

history

of

breast cancer, history

of

benign

breast disease, ages at menarche and menopause,

lac-tation,

drinking

habits and

height

were not

significant-ly

related

to breast cancer

risk.

DISCUSSION

In

our study, there

is

one

important

methodological

lirnitation.

Our

control

series

rnight

rnore

prevalêntly

include women

with

benign breast disease than general

female

population,

because

we

selected,

though

ran-domly,

the

controls from women

who sought

forbreast

examination at the

department

of

breast

surgery

and

were later

proved not to

have breast

anllcer.

Accord-ingly,

when

a

potential risk factor for

breast cancer is

positively

associated

with

the risk

of

benign

breast disease,

then

the

RR

obtained

for

such a

factor rnight

be

conservative.

Conversely,

the

risk

for breast cancer

might

be over-estimated, when

a

potential risk

factor

for

breast cancer

is

negatively

linked

to

the risk of

benign

breast disease.

Farnily

history

of

breast cancer

is

cottsisteutly

in-crirninated

as a

risk factor for

female

breast cancer.lS

Our failure

in

finding

an association between

breast

cancer and

family history

may

be

partly

ascribable to

the excessive

inclusion of

wornen

with

benign

breast disease

in

our control

series,

since family history of

breast cancer is

knowu

to be

positivelv

associated

with

the

history of

benign

breast

àir"ur".27'28

Both early

menarchel'5'9-12 andlate

menopause2-4'10' l1'13 _are

well-established

risk factors.

In

_Jàpan,

how-ever,

significant

relevance

of

early

rnenarche and late lnenopause

to

breast cancer

risk

has

not always

been detected,S'19

likewise

our study.

Decreasing

risk of

breast caucer

with

increasing

dura-tion of

rnenstrual

cycle

has

been

suggested

in

some stuclies,l'29 as

clid

our

study.

We

foùna

a

significant

association

between regular

rnenstrual

cycle

and

an

increased prernenopausal breast caucer

risk, but

this

was

not

detected

in

previous

studies.l9

These

two

particular findings on mer$truation

tnay suggestively

indicate that

breast

cancer

risk

appears

to

be

directly

related

to

the

cumulative number

of

regular

ovulatory

cycles.29'30

I-ate

age at

first

birth/full-term

pregn4qcJ_is.known to

be linked

to

breast cancer

ri;k.r'3-6'8'q'12'14'15

our

study

also detected a

significantly

larger

RR for

later

age

at first

birth,

particularly

in

postmenopausal

women.

Several recent studies

have noted that frequent

full

term

pregnancy

or

birth

has a

protective

effect

against breast

cancer, independently

of

age

at first birth/full

term pregnancy.l'10'14

In

our sùdy

also,

an

inde-pendent and

significant

trend

of

decreasing

risk with

increasing

number

of

livebirths was

observed,

par-ticularly

in

premenopausal

women. This finding

may

essentially

indicate that

a recently

increasing

breast cancer incidence in Japan is

partly

related to the

rapidly

declined

birth rate.'r

Premenopausal women

who

had ever lactated were

not

found

to

be at a significantly smaller

risk of

breast cancer

by

the

multivariate

analysis.

An

association between

smoking habits and

breast

cancer

risk remairs

inconclusive. Most

studies

have founcl

no clear

association,3'8'20'22

while

some

inves-tigators

have suggested an

unfavorable effect of

smok-ing

traUits

on

breast

.un

"r.r9'21

In

the

present study,

smokiug

habits was

found

to be associated

with

breast

carcer risk, likewise a previous study

conducted

in

Nagoya,

Jupuu.lg

The

RR for

current smokers

in

our

study, particularly

in

postmenopausal

women, might

be

over estimated, possibly

due

to

the

potentially

ex-cessive

number

of

women

with

benign

breast disease

in

our

controls, since benign breast disease

was reported as

negatively

associated

with

smoking

habits in postrnenopausal wàme n.28'32

In

our study, we

failed

to detect dose-response

relationship

between the

num-ber of cigarettes smoked per day and breast cancer

risk.

A

positive

associarion berween

atcohol -"i},Tp,rtjlrtÀ

and breast cancer has been reported

in

many, :

but not

all,2'5'ts'to epidemiological

studies.

The preseut

study,

however,

did not show

a

significantly

larger RR

for

current drinkers.

Obese

women

were

at significantly

greater

risk

of

postmenopausal breast cancer,

which

is

in good

a9ree-ment

*itn

previous

finaings.l'8'1fi6'17

"

In

prelnenopausal

women,

a

significant

trend

of

increas-ing

breast cancer

risk

with

increasing

weight

was

ob-served. This findiug might,

however, be attributable

to

excessive

inclusion of

benign

breast disease

in

our

Vol 4, No 3, July - September 1995

prevalent

in

prernenopausal

worneu and obesity

is

negatively

associated

with

the

risk

of

this

dis-ea;e.27 '28'13

Several

studies have

reported

a positive

associatiou

between height and fernale

breasi.un""r,l1'34

but

we

did

not

find

such an association.

CONCLUSION

Our study disclosed the

following

rnajor

findings:

(a)

the rnore the nurnber

of

livebirths, the smaller

the

female breast cancer

risk,

particularly

in

prernenopausal

women; (b) in

premenopausal

women,

regular rnenstrual cycle

significantly

increased

the

risk,

aud

its increasing duration

decreaserl the

risk;

(c)

current

srnokers experienced a

significantly

larger RR,

particularly

in

postmenopausal wornen;

(d)

obese

women

were

at a significantly

greater

risk

of

postmenopausal

breast

cancer; (e) the later the

age at

first

livebirth, the higher the

postmenopausal

breast

cancer

risk;

(f)

family history

of

breast cancer,

history

of

benign

breast disease, ages

at

menarche

and

lnenopause,

lactation,

drinking

habits and

height

were

independently

not associated

with

female breast cancer

risk.

Acknowledgments

The authors are

grateful

to the nurses and

public

health

llurses

for

excellent

care

aud data collection

of

the

breast

callcer

cases and

controls.

This

work

was supported

by

the

Ministry of

Education

and Culture,

Japan, Grants

No.

01042007

and

04042013; and was

partly

supported

by

the

Indonesian

Caucer

Fouudation. This collaborative

study was a part

of

Special Cancer

Research

Project

in

Monbusho

[n-ternational

Scientific

Research

Prograrn,

with

the

ap-proval

of

the Dean,

Faculty of Meclicine,

University of

Indonesia, No. 4383ÆT02.H4.FIÇE/88.

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