IJC

International Journal of Cancer

Risk factors for breast cancer among Filipino women in Manila

Lorna J. Gibson1, Clarisse Hery2, Nicolas Mitton3, Abigail Gines-Bautista4, D Maxwell Parkin5,
Corazon Ngelangel6 and Paola Pisani7
1

Cancer Research UK Epidemiology and Genetics Group, London School of Hygiene and Tropical Medicine, London, UK
International Agency for Research on Cancer, Lyon, France
3
Registre du Cancer de lIse`re, Meylan, France
4
WHO Regional Office for the Western Pacific, Manila, Philippines
5
Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom
6
Department of Clinical Epidemiology, College of Medicine, University of the Philippines, Manila
7
Cancer Epidemiology Unit, University of Turin, Turin, Italy
2

When this study was carried out, around 1995, age-adjusted incidence rates of breast cancer varied more than 10-fold worldwide.1 Generally, the highest rates are found in the typically westernised countries of North America and Europe, whilst much
lower rates are observed in Asian and African populations.2
An exception to the normally low breast cancer incidence
in Asian women has been reported for the Manila Cancer
Key words: epidemiology, breast cancer, risk factors, Philippines
Abbreviations: ASR: age standardised incidence rate; CBE: clinical
breast examination; OR: odds ratio; CI: condence interval; FFTP:
rst fullterm pregnancy; BMI: body mass index; PEM: protein
energy malnutrition; OC: oral contraceptive; SES: socioeconomic
status
Grant sponsor: US Army Medical Research and Material
Command; Grant number: DAMD17-94-J-4327; Grant sponsor:
Cancer Research UK programme; Grant number: CR-UK-C150/
A5660
DOI: 10.1002/ijc.24769
History: Received 26 Mar 2009; Accepted 6 Jul 2009; Online 22 Jul
2009
Correspondence to: Lorna J. Gibson, Cancer Research United
Kingdom Epidemiology and Genetics Group, London School of
Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT,
United Kingdom, Fax: 0207 580 6897, E-mail: lorna.gibson@lshtm.ac.uk

C 2009 UICC
Int. J. Cancer: 126, 515521 (2010) V

Registry in the Philippines where, at 55.1 per 100,000, the

age standardised (world) incidence rate (ASR) truncated at
age 74, over the period 1993972 when our study was carried
out, was similar to the 52.0 per 100,000 rate seen in the UK
in 1983-87, before the introduction of screening.3
The reason for this high breast cancer rate in Manila is
unknown but may be associated with the change in lifestyle
that has occurred in urban Manila since the 1960s. As countries become more westernised, the patterns of cancer
incidence change. Westernisation comprises the decline in
fertility rates, change in diet and decreased physical activity.
Singapore, for example, underwent a dramatic transformation
in the 30 years following World War II, and this transition
was accompanied by changes in the rates of cancer,4,5 including breast cancer, that has been attributed to the major shift
in reproductive and other lifestyle patterns.6 The decline in
fertility rates has been the major factor in the increase in
breast cancer incidence in afuent countries. Given this, the
observed high rate of breast cancer in Filipino women, especially amongst the young, is unexpected.
The purpose of this study was to evaluate, in a population
characterised by high fertility rates, the increase in breast
cancer risk associated with some of the known risk factors
that are determinants of the high incidence in Western
countries.

Epidemiology

Age-adjusted incidence rates of breast cancer vary greatly worldwide with highest rates found in the typically westernised
countries of North America and Europe. Much lower rates are observed in Asian and African populations but an exception to
this has been reported for the Manila Cancer Registry in the Philippines. The reason for this high rate is unknown but may be
associated with the change in lifestyle that has occurred in urban Manila since the 1960s. In 1995, a randomised controlled
trial was set up in Manila to evaluate the feasibility of a screening intervention by clinical breast examination as an
alternative to mammography. The cohort of 151,168 women was followed-up to 2001 for cancer incidence and a nested
case-control study carried out. This aimed to evaluate the increase in breast cancer risk associated with known risk factors.
Increased risks were seen for a high level of education (OR 5 1.9 95%CI 1.13.3 for education stopped at
13 versus <13
years), nulliparity (OR 5 5.0 95% CI 2.510.0 for nulliparity versus five or more children), and late age at first birth (OR 5
3.3 95% CI 1.38.3 for age
30 versus <20 years). We found no association with excess body weight, height, use of
exogenous hormones or alcohol consumption. From this study, the recognised classical risk factors do not fully explain the
high breast cancer incidence in Metro Manila, especially when compared to other urban Asian populations. We conclude that
it is too simplistic to ascribe the high risk to westernisation.

Breast cancer risk factors in filipino women

Epidemiology

516

Material and Methods

Lifestyle factors

The study is a case-control design, nested within a large

intervention cohort recruited in the Manila resident population. In 1995, a randomised controlled trial was set up in
twelve municipalities of Metro Manila, comprising 202 health
centres, in areas covered by the Philippine Cancer Society
Manila (ManilaPCS) and the Department of HealthRizal
(RizalDOH) Cancer registries. The aim of the trial was to
evaluate the feasibility of a screening intervention by clinical
breast examination (CBE) as an alternative to mammography
and assess whether this led to a subsequent reduction in
mortality.7 During the period 19951997, 151,168 eligible
women aged 3564 years were interviewed and offered CBE.
Of those interviewed, 138,392 (91.5%) accepted the examination. Young women were included because of the high number of breast cancer cases below age 50.2 The participants
were interviewed and examined by trained nurses at their
place of residence or local health centre. Questions covered
demographic and socio-economic details, reproductive history, self-reported weight and height, family history of breast
and ovarian cancer, and consumption of alcohol and tobacco.
The cohort was followed-up to 2001 by the two cancer registries for cancer incidence and vital status of all cases. The
case-nding procedures of both registries were enhanced to
reduce the time to registration, and cases identied during
the follow-up period linked to the cohort.7
This nested case-control study included 123 incident
breast cancer cases identied in the intervention cohort of
151,168 women to the end of 2001, 32 of which had been
detected through the screening process. For each cancer case,
eight controls were chosen at random from the intervention
cohort, to match cases by municipality of residence, date of
CBE (6 3 months), and age (6 3 years); 978 controls were
selected. In 2001, an attempt was made to contact cases and
controls to assess vital status and, if alive, re-interview them
using the same questionnaire. Of these, by case and control
status, respectively, 29% (36) and 49% (480) had moved and
could not be traced; 42% (52) and 2% (20) had died; 7% (8)
and 12% (114) refused the interview; the remaining 22% (27)
and 37% (359), were re-interviewed. This second interview
was used to determine the reproducibility of the questionnaire and the information from the two questionnaires was
pooled. The proportion of records having missing information, however, remained high.
We used unconditional logistic regression in STATA 10
(Stata Corporation, College Station, TX) to estimate odds
ratios (ORs) and 95% condence intervals (CI) for individual
variables. Crude ORs were adjusted only for age and municipality. All P values are two-sided.

In this study population, 18 cases (14.6%) and 142 controls

(16.3%) were overweight or obese, dened as having a body
mass index (BMI) of 25 Kg/m2 or greater. Of these, only
three (2.4%) cases and 13 controls (1.3%) were obese (BMI

30 Kg/m2 or greater). Once adjusted for education and
parity, we observed no relationship between BMI and breast
cancer risk either overall or by menopausal status (Table 1).
The adjusted ORs were 1.1 (95% CI 0.34.1) in premenopausal women and 0.8 (95% CI 0.32.2) in postmenopausal
women, not statistically signicant.
The mean height of cases and controls was 155.5 cm and
155.2 cm, respectively. There were only eight women (one
case) over 168 cm, approximately 50 600 . We observed no
increase in risk with increased height in 5 cm increments.
Alcohol consumption was rare in these women with 93.5% of
cases and 89.8% of controls being non-drinkers. The prevalence of tobacco smoking was also low, and the proportion of
women in each group who had never smoked was similar
(89%). Neither smoking nor drinking was associated with the
disease.
Reported family income was low by Western standards,
ranging from 400 to 80,000 pesos per month (at the time of
the study, the exchange rate was US$1 30 pesos) with per
capita income (family income divided by the number of
cohabitants) varying from 50 to 30,000 pesos. This variable
was not associated with the risk of breast cancer. Conversely,
educational level, which can also be used as a proxy for SES,
was a signicant predictor of risk. Cases were more educated
than controls (Table 1) with 18.7% completing a tertiary education compared with 14.1% controls. The risk of breast cancer almost doubled for women who had received a tertiary
education compared with those receiving only minimal education (OR 1.8, 95% CI 1.03.6). Breast cancer risk also
increased for those who continued education after 13 years
of age (OR 1.9, 95% CI 1.13.3).

Results
The mean age of the 123 cases and 978 controls was 47.9
and 47.8 years, respectively.

Reproductive factors

Cases were more likely to be nulliparous (25.2% vs. 13.5%),

have their rst full-term pregnancy (FFTP) at age 30 or over
(16.3% vs. 7.2%) and have an age at menarche below 13 years
(30.9% vs. 25.9%) though the mean age at menarche was
similar (13.5 vs. 13.7 years) (Table 1). There was a non-statistically signicant decrease in breast cancer risk with a later
age at menarche (p 0.49). Age at FFTP and parity were
the only variables strongly associated with breast cancer.
When analysed separately, the ORs declined steadily to 0.2
(95% CI 0.10.4) for ve or more pregnancies compared to
none. Among parous women, the ORs increased with
increasing age at FFTP (p for trend <0.001) reaching an OR
of 5.4 (95% CI 2.312.8) in those who had their rst child at
age 30 or over. Compared to an early pregnancy, nulliparous
women had a risk similar to that of women aged over 30 at
FFTP (crude OR 4.4, 95% CI 2.09.8). When parity and age
C 2009 UICC
Int. J. Cancer: 126, 515521 (2010) V

Table 1. ORs for breast cancer, adjusted for age and municipality (*); adjusted for age, municipality, parity, age at FFTP, education (y)
Case
(n 5 123)

Variable

n
Age stopped education

Level of education

Age at menarche

Premenopausal

13

71

57.7

521

53.3

1.9

1.23.0

missing

18

14.6

27

2.8

9.6

4.719.6

minimal

39

31.7

482

49.3

1.0

43

35.0

331

33.8

1.7

1.02.8

tertiary

23

18.7

138

14.1

2.2

1.24.0

missing

18

14.6

27

2.8

9.2

4.618.6

mean [SD]

13.5 [1.8]

OR

95%CI

p value

ph < 0.001

1.9

1.13.3

ph 0.020

1.0

pt < 0.001

1.8

1.03.0

1.8

1.03.6

pt 0.049

0.51.4

ph 0.492

13.7 [1.7]

<13

38

30.9

253

25.9

1.0

13

84

68.3

714

73.0

0.8

1.0
0.51.2

ph 0.235

0.8

0.8

11

1.1

31

25.2

132

13.5

1.0

12

30

24.4

171

17.5

0.7

0.41.3

0.4

0.21.0

34

34

27.6

287

29.3

0.5

0.30.9

0.4

0.20.9

19

15.4

311

31.8

0.2

0.10.4

0.2

0.10.4

7.3

77

7.9

0.5

1.38.6

7.3

159

16.3

1.0

27

22.0

307

31.4

1.6

<20

1.0

17

13.8

178

18.2

1.7

0.74.1

20

16.3

70

7.2

5.5

2.312.9

nulliparous

31

25.2

132

13.5

4.6

2.110.3

missing

19

15.4

132

13.5

3.3

1.18.4

pre

78

63.4

632

64.6

1.0

post

37

30.1

290

29.7

1.1

6.5

56

5.7

103

83.7

831

85.0

1.0

ever

16

13.0

125

12.8

1.0

3.3

22

2.2

<25

92

74.8

722

79.0

1.0

25

18

14.6

142

16.3

ph 0.771

ph 0.948

1.0

0.61.6

ph 0.898

1.35.2

13

10.6

114

4.7

2.6

74.4

511

80.9

1.0

25

12

15.4

93

14.7

1.1

0.62.2

10.3

28

4.4

3.3

1.38.1

<25

30

81.1

217

74.8

1.0

25

16.2

57

19.7

0.8

2.7

16

5.5

89.4

878

89.8

1.0

ever

13

10.6

87

8.9

1.2

0.0

13

1.3

115

93.5

878

89.8

1.0

yes

6.5

83

8.5

0.7

missing

0.0

17

1.7

0.52.9
1.38.3

pt 0.032

0.62.8

ph 0.593

0.41.8

ph 0.595

1.0

0.51.7

ph 0.945

1.0

0.42.7

1.3

0.8

1.0

58

110

1.2
3.3

1.0

<25

ph, p-value for heterogeneity; pt, p-value for linear trend.

pt < 0.001

0.62.9

1.0
0.52.0

missing

no

1.3

0.61.8

never

pt < 0.001

1.0

30

never

pt < 0.001

0.73.5

2529

missing
Drinker

p value*

1.0

vocational/high
school

missing
Smoker

95%CI

1.0

missing
Postmenopausal

OR

44.0

missing
BMI

430

missing
OC use

27.6

2024

Menopausal status

34

missing
Age at rst birth

Adjusted

Crude*

<13

missing
Parity

Control
(n 5 978)

1.0
ph 0.656

1.1

0.52.2

1.1

0.34.1

ph 0.817

1.0
0.32.1

ph 0.601

0.8

0.32.2

ph 0.531

0.62.9

ph 0.486

0.21.5

ph 0.191

1.0
0.62.3

ph 0.571

1.3

0.31.6

ph 0.387

0.5

1.0

Breast cancer risk factors in filipino women

518

Table 2. ORs for breast cancer by parity and age at rst full-term
pregnancy compared with nulliparous adjusted for age, municipality
and education
Age at rst live birth
Parity

<20

2029

301

0.5

0.3

0.8

Nulliparous*
13

OR
95%CIs

0.21.5

0.10.7

0.41.5

45

OR

0.3

1.1

0.2

95%CIs

0.032.0

0.52.3

0.10.9

OR

0.1

0.2

0.4

95%CIs

0.040.5

0.10.4

0.11.1

Epidemiology

*Reference category.

at FFTP were adjusted for each other, the OR associated with

age at FFTP of 30 or over was substantially reduced (OR 3.3,
95% CI 1.38.3), while the protection due to parity was unaffected and women with ve or more children had one fth
the risk of nulliparous women. The risk decreased with
increasing numbers of births (p for trend <0.001). Table 2
shows the ORs for combinations of parity and age at FFTP,
adjusted for age, municipality and education, with nulliparous as the reference group. We observed a strong protective
effect of ve or more pregnancies at all levels of age at FFTP
although the risk reduction was largest among women who
had their rst child before age 20 (OR 0.1, 95% CI 0.040.5).
As the questionnaire only asked about current breastfeeding, we were not able to assess breast feeding as a risk factor
in our analysis. There was no relationship between increased
breast cancer risk and age at last childbirth (p 0.30). There
was a non-signicant increase in risk (OR 1.5, 0.83.0) with
any preterm pregnancies (abortions or miscarriages) versus
none, but this question was only answered by half the participants. Oral contraceptive (OC) use was not widespread
amongst women in the study with only 13% reporting a positive history of use. Among women who had used contraception, nearly half reported OC use. There was no evidence to
support an increased risk with OC use. Slightly more cases
were premenopausal (57.7% vs. 63.6% for controls) and there
was some indication of an increased risk of breast cancer in
those women who reported being postmenopausal for less
than ve years (OR 2.6, 1.16.3).
Of the total intervention cohort of 138,392 women, 3000
(2%) reported a positive family history of breast or ovarian
cancer. The proportion was similar (2.4%) in this nested
case-control study although 25% cases and 17% controls did
not answer this question. Previous benign breast disease was
reported by 28 women and could not be evaluated.

Discussion
We report on the relationship between reproductive and lifestyle factors and breast cancer risk in an urban population of
South East Asia. The recognised classical risk factors do

not explain this high incidence in comparison to other Asian

populations and, in particular, other urban populations such
as Bombay and Shanghai. Women in Manila still have fertility rates that are greater than other Asian populations,
including Japan, where breast cancer rates are signicantly
lower.
Cancer is the third leading cause of morbidity and mortality in the Philippines.8 In 2002, there were an estimated
13,000 new cases annually,9 of which 80% had regional
involvement at presentation,7 leading to around 7600 deaths
each year. Breast carcinoma is the most common malignancy
in women, and the second most common after lung cancer
in the population, constituting roughly 13% of all cancer
cases.8
An unusually high incidence of breast cancer in comparison to rates in other Asian regions, has been observed. The
rate in Manila is considerably in excess of the more typical
gures seen in other Asian cities for the same period: Osaka
Prefecture 27.8; Bangkok 25.2, Hanoi 23.3 (aged to 65); Seoul
21.9; Shanghai 26.7; Hong Kong 34.3 per 100,000. Incidence
is particularly high in the younger age groups, approaching
or even exceeding UK rates (22.1 cancers per 100,000 women
aged 3034 in Manila compared with 22.0 in England and
Wales, 11.8 in Osaka, 13.8 in Hanoi, 15.2 in Bangkok, 14.7
in Shanghai and 19.3 in Hong Kong.
Of the factors investigated, only parity, age at FFTP and
educational level were associated with breast cancer risk in
this population. The main limitation of our study was the
relatively high proportion of missing data in some of the
exposures that are normally quite reliably reported, e.g., miscarriages. A certain level of misclassication may have
reduced the strength of the estimated associations but it is
unlikely that this caused bias as the interviews were conducted before the onset of the disease. The strengths of the
study are the absence of differential misclassication bias and
a high degree of representativeness of the study base since
the cohort was recruited in a population-based survey.
In economically advanced countries, breast cancer risk is
known to increase with early menarche, late menopause, low
parity and delayed rst pregnancy.10 Other reproductiverelated factors associated with the disease include the use of
OCs11 and hormone replacement therapy,12 and breastfeeding.13 Lifestyle factors inuencing breast cancer risk include
excess body weight in postmenopausal women,14 diet15 and
alcohol consumption.16 Certain benign breast diseases,17 a
family history of breast cancer,18 height,19 and SES20 are also
risk factors.
We found no association between BMI and breast cancer
risk in either pre- or postmenopausal women, albeit the latter
group was based on small numbers. A recent meta-analysis
has shown that, whereas in Western countries, BMI is inversely associated with premenopausal breast cancer risk but
positively associated with postmenopausal breast cancer, in
the Asia-Pacic region increased BMI is positively associated
with both pre- and postmenopausal breast cancer.21
C 2009 UICC
Int. J. Cancer: 126, 515521 (2010) V

We conrm the protective effect of full-term pregnancies, which was greater the earlier age at FFTP, These
results are similar to those found in other populations
although the strength of the association appeared somewhat
stronger than in Western populations where relative risks
for ve or more children are half of that for nulliparous
women.6,2224 None of the other reproductive factors investigated had a statistically signicant association with the
disease. A previous study carried out in 199425 showed
similar results to our study. As parity and age at rst birth
have been shown to be risk factors in this Filipino population, it is of interest to consider possible reasons for both
the high rate compared to other Asian populations and the
increasing trend.
Although fertility in the Philippines has been falling since
the 1950s,26,27 the total fertility rate (TFR) in the 1990s was,
at 3.5, still higher than the TFRs of other Asian countries
with lower breast cancer rates. For example Malaysia, Indonesia, Vietnam, Thailand and Singapore had TFRs of 3.2,
2.8., 2.3, 2.0 and 1.7, respectively.26 There is also wide regional variation within the Philippines. Using the 19911993
specic fertility rates, the overall TFR was 4.1 but this varied
between 2.8 in Manila to 5.9 in rural Bicol28 and had fallen
to 2.5 in Manila by 1998; this is still higher than in European
populations.
Two major determinants of fertility are age at marriage
and contraceptive practices. There has been little change in
age at rst marriage and, in this aspect, the Philippines differs from most other Asian societies. Age at marriage is
rather late but, as it has changed little over time (23.4, 24.5
and 23.8 years in 1968, 1978 and 1988, respectively), it is
now lower than in some neighbouring Asian countries where
the age at marriage has risen steadily over the same period.26
In the same time period, there has been a threefold increase
in contraceptive use although use of hormonal contraception
remains a rather uncommon practice; according to the 1995
census survey, only 11.2% of the female population were
users.29 It is interesting to note that there is also a relatively
high proportion of women in the Philippines who remain
childless at the end of their reproductive years (estimated to
be 910% compared to 34% in other Asian societies).26 Nulliparous women represented 13% of our cohort of Manila
residents.
Breast cancer is more common in more afuent societies
as well as in women of higher SES level within populations.30
In our study, when income was used as a proxy for SES, it
was not associated with risk, but when educational level was
used as a proxy, there was a signicant increase in risk.
Breast cancer incidence is rising in many countries including
those in Asia where previously risk was low.1 In populations
of south and east Asia, increases in rates range from 1 to
3.6% per year5,3133 and are often more marked in younger
generations of women.1,34,35 In many countries in Asia, for
example Korea, Taiwan, Singapore, society has changed
markedly in the past 30 years due to rapid economic develC 2009 UICC
Int. J. Cancer: 126, 515521 (2010) V

519

opment and the corresponding increase in standard of living.

In western countries, increasing SES is a risk factor for breast
cancer.30 Although urbanisation has been rapid with 52% of
the population living in cities in 1996 compared to 33% in
1970,36 the Philippines have not experienced the same economic boom as many other countries in their region. Therefore the incidence of breast cancer cannot be explained by
improved SES.
In Filipino women in Hawaii, a study examining trends of
breast cancer incidence and risk factor prevalence over 25
years observed changes in reproductive behaviour and
increasing obesity.37 It is well-established that when Chinese,
Japanese, or Filipino women migrate to the US, their breast
cancer risk rises with each subsequent generation until it
approaches that of Caucasians living in the US, indicating
that exposures rather than genetics are involved.38 Incidence
rates of Filipinos in the US39 and California40 are rather
higher than those of other Asian-origin groups, despite the
fact that most are relatively recent immigrants to the US.41
One possible hypothesis is that the lifestyle with respect to
eating habits in Metro Manila, especially among those of
higher SES, resembles that of cities in the US, and so the
effect of citizens from rural areas moving to Manila is similar
to migration to the US. The US colonised the Philippines
from 1899 to 1940 and is still a considerable inuence today
in many aspects of life. There have been found to be modest
but positive associations between consumption of rened carbohydrates and breast cancer risk.42 There is a plethora of
US-style fast food outlets, high-calorie soft drinks are widely
consumed and so the diet of many inhabitants of Metro
Manila may resemble that of the US rather than rural
Philippines.
Which components of diet affect breast cancer risk and
how they do this remain poorly understood. The most authoritative and recent review of the subject identied only
excess body weight and lack of physical exercise, or energy
balance, as clear determinants of the disease.43 In this population, obesity was rare and overweight uncommon; however
incidence rates of breast cancer were already high when the
study was conducted. Our results conrmed that excess body
weight was not a major determinant of risk in this population. Use of hormonal treatment for menopausal symptoms,
and use of other exogenous hormones were negligible. In
addition, 91% of Filipinas living in urban areas were lifelong
alcohol abstainers (90% in our study).44
Our work shows that it is simplistic to ascribe increasing
rates of breast cancer in low- and middle-income countries
to the westernisation of lifestyles. This fails to recognise that
there are already substantial differences in breast cancer risk
in those populations which are not obviously explained by
differences in those habits that dene westernisation. For
this reason, aetiological research in Asian and other middleincome countries offers a powerful opportunity to test
hypotheses developed in high risk populations and thus could
provide much needed new ideas.

Epidemiology

Gibson et al.

Breast cancer risk factors in filipino women

520

Acknowledgements
The study was funded by the US Army Medical Research and Material
Command, grant number DAMD17-94-J-4327. Lorna Gibson is
supported by Cancer Research UK programme grant number CR-UK-

C150/A5660 and would like to thank Julian Peto and Isabel dos Santos
Silva for allowing her time to work on this paper, as well as their
invaluable comments. The authors thank the staff of the Manila and
Rizal Cancer registries.

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