948899
research-article20202020

PSH0010.1177/2010105820948899Proceedings of Singapore HealthcareTokutake et al.

PROCEEDINGS

Short Communications

OF SINGAPORE HEALTHCARE

Age-specific incidence rates of breast
cancer among Japanese women increasing
in a conspicuous bimodal distribution
pattern

Proceedings of Singapore Healthcare
﻿1­–4© The Author(s) 2020
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https://doi.org/10.1177/2010105820948899
DOI: 10.1177/2010105820948899
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Nanami Tokutake1, Riona Ushiyama1, Kyoka Matsubayashi1and Yuji Aoki2

Abstract
Breast cancer incidence rates are increasing in East and Southeast Asia, along with the westernisation of reproductive andlifestyle patterns. Such westernisation is thought to be involved in the cumulative exposure of breast tissue to both endogenousand exogenous oestrogen. Immigrant studies among Asian American women indicate that risk factors for breast cancer can be
modified. When breast cancer incidence rates were compared with those of corpus uteri and colon among Japanese womenin 2005, 2010 and 2015, it is of note that age-specific incidence rates of breast cancer in 5-year age groups clearly increased
during the 10-year period in a bimodal distribution pattern, with two peaks in the 45–49 and 60–64 years age groups. From
the relevant literature, it is inferred that the low prevalence of obesity and the intake of soy products or isoflavones among
Japanese women may contribute to the bimodal distribution pattern by suppressing the extent of increase in breast cancer
incidence rates among Japanese postmenopausal women. With regard to dietary habits relating to obesity, it has been globally
reported that the intake of high-calorie foods is associated with the incidence of oestrogen receptor-positive breast cancer
in both pre- and postmenopausal women, while high-carbohydrate or -milk intake that can enhance the secretion of insulin
or insulin-like growth factor 1 is associated with that of oestrogen receptor-negative breast cancer mostly in postmenopausal
women. Studies are needed to clarify the aetiology or modifiable factors behind the bimodal incidence rates of breast cancer
among Japanese women.
Keywords
Breast cancer, age-specific incidence, obesity, dietary habits, menopausal status

Introduction
Breast cancer has been reported to be the most frequently
diagnosed cancer in the vast majority of countries (154/185),with an estimated 2.1 million cases in 2018. The incidence
rates of breast cancer are generally high in North America
and Western Europe, and low in most of Africa and Asia.1
The age-specific incidence rates in Asian countries differ fromthose in Western countries. The Breast Cancer Working
Group described that while the incidence of age-specificbreast cancer increased with age in Western countries, it
showed a bell-shaped pattern in Japan and Korea, with a peakin the 40–50 years age group and a flatter pattern after the
peak in Singapore and the Philippines, using estimates of theworldwide cancer incidence for the year 2002.2 The Working
Group anticipated that the age-specific incidence patterns in
Asian and Western countries would approach those seen in
Singapore. Oestrogen is thought to play an important role inthe development of breast cancer.3 Breast cancer incidence
rates are increasing in East and Southeast Asia, along with thewesternisation of reproductive and lifestyle patterns which
can be involved in the cumulative exposure of breast tissue toboth endogenous and exogenous oestrogen.4,5
In this short communication, we demonstrate that the agespecific incidence rates of breast cancer among Japanesewomen are increasing in a conspicuous bimodal distribution
pattern, with two peaks in pre- and postmenopausal age groups.

1Department of Health and Nutritional Science, Matsumoto University,

Japan
2Graduate School of Health Science, Matsumoto University, Japan

Corresponding author:
Yuji Aoki, Graduate School of Health Science, Matsumoto University, 20951 Niimura, Matsumoto, Nagano 390-1295, Japan.
Email: yaoki55@t.matsu.ac.jp

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons
Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use,
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Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Proceedings of Singapore Healthcare﻿

Figure 1. Age-specific cancer incidence rates (per 100,000 population) of the breast, corpus uteri and colon among Japanese womenin 5-year age groups in 2005, 2010 and 2015, respectively, using national estimates from Cancer Information Services, National Cancer
Centre, Japan.

The aetiology behind the bimodal incidence rates of breast cancer is speculated by the relevant literature in association withmodifiable factors, including dietary habits.

Results and discussion
Figure 1 shows that age-specific cancer incidence rates (per100,000 population) of the breast, corpus uteri and colon
among Japanese women in 2005, 2010 and 2015, respectively, using national estimates from Cancer Information
Services, National Cancer Centre, Japan. It is of note that theage-specific incidence rates for breast cancer in 5-year age
groups clearly increase during the 10-year period in a bimodal
distribution pattern, with two peaks in the 45–49 and 60–64
years age groups. The cancer incidence of corpus uteri, whichis also thought to be affected by oestrogen,6 was lower thanthat of breast cancer, but it still increased during the same
period in a bell-shaped pattern, with a single peak in the 55–
59 years age group. By contrast, the increase with age of theincidence of colon cancer, which was somewhat similar tothat of breast cancer in Western countries, reduced 2015, as
had been predicted by the Research Group for Populationbased Cancer Registration in Japan.7 The three distinct patterns of age-specific cancer incidence rates among Japanesewomen are intriguing to presume the aetiology for breast
cancer in relation to the westernisation of reproductive andlifestyle patterns. Modifiable risk factors for breast cancer,
including pregnancy history, use of hormone replacement
therapy and obesity assessed by body mass index (BMI), arealso indicated by the increased incidence of breast cancer
among immigrant Asian American women.4
From the two-component mixture models, it is inferredthat bimodal age-specific distributions of breast cancer incidence vary with the proportional composition of pre- andpostmenopausal components, regardless of molecular characteristics.8 A study examining breast cancer incidence during
the period 1978–1997 in the USA and Japan9 showed that
Caucasians and African Americans had a bimodal (early- andlate-onset) breast cancer population and that Japanese in
Osaka Prefecture had only an early-onset breast cancer population. Age-specific breast cancer incidence rates among
Japanese Americans in Hawaii were high but resembled thoseamong native Japanese in Osaka in the earliest calendar period(1978–1982), and increased up to those among Caucasians
and African Americans, especially among postmenopausal
women, for subsequent calendar periods. The authors speculated that the difference in breast cancer incidence rates
between Americans and Japanese was partially ascribed to amuch lower prevalence of obesity in Japan than in the USA
and to screening mammography that was not implemented
until 2000 in Japan. It was of interest that the age-specificbreast cancer incidence rates among Japanese Americans in
Hawaii during 1978–1982 appeared to be a bimodal distribution pattern in the semi-log graph. As it was considered thatthe prevalence of overweight and obese people was very low
in Japan,10 we examined the associations of obesity with thebimodal distribution pattern with the conspicuous two peaks
among Japanese women shown in the present study.
In Figure 2, the age-specific incidence rates of breast cancer are shown when regrouped by a 10-year period insteadof a 5-year period in order to be in accordance with the agespecific prevalence rates of obesity (BMI ⩾25 kg/m2) among
Japanese women without pregnancy or lactation reported by
National Institute of Health and Nutrition, Japan. It is first recognised that the conspicuous two peaks of the age-specificdistribution of breast cancer incidence have been hidden
when regrouped by the 10-year period. Referring to previous
epidemiological cancer studies, the age-specific prevalence
rates of obesity 10 years before the year when the breast
cancer incidence rates were obtained are used for comparison. Both the breast cancer incidence rates and the obesity
prevalence rates appear to be in parallel among whole agegroups. However, the obesity prevalence rates of the 30–39
years age group only increases from 1995 to 2005 in parallelto the increase in the breast cancer incidence in the 40–49
years age group. The obesity prevalence appears to decrease
after 40 years of age, which may contribute to the reason
why breast cancer incidence rates among Japanese postmenopausal women did not increase up to those among JapaneseAmerican postmenopausal women described above. The
obesity prevalence rates in the 60–69 years age group were31.0% in 1995, 31.0% in 2000 and 29.1% in 2005. In 2015, theage-specific prevalence rates of obesity increased to 11.1%(BMI ⩾30 kg/m2, 2.6%) at 20–29 years of age and decreased

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Tokutake et al.

Figure 2. Comparison of (a) the age-specific incidence rates (per 100,000 population) of breast cancer among Japanese women in
10-year age groups with (b) the age-specific prevalence rates (%) of obesity (body mass index ⩾25) 10 years before the year when thebreast cancer incidence rates were obtained. National data obtained separately from National Cancer Centre and from the National
Institutes of Health and Nutrition.
Table 1. Associations between breast cancer incidence and dietary habits, stratified by menopausal status and, if assessed, oestrogenreceptor (OR) expression status.
Authors and year Countryof publication

Study

Marzbani et al.
2019

Iran

Case control

Kim et al. 2017

Korea

Cohort

McCann et al.
2017

USA

Case control

Shin et al. 2016

Japan

CohortDe Cicco et al.
2019 (Review)

Italy

CohortEuropeCohortPremenopausal

Postmenopausal

OR (+)OR (–)

OR (+) OR (–)•

Not assessed••

USA+Europe Cohort

•
•
•
•

•

•
•

•

USA+Europe Prospective
Asia

Case control•

Ref. no.

Consumption of soft drinks, industrial 11
juices, sweets and fried foods;
inadequate consumption of vegetables••

Breast cancer risks in association withdietary habits

Consumption of grilled meat
Irregular eating habits

12High milk intake
Negative association with sweet dairy
intake13

Westernised dietary pattern: highintake of meat, processed meat,bread, dairy products, coffee, softdrinks, tea, sauces and alcohol

14

Negative association with intake of
15
fruits and vegetables
High total and saturated fat intake
Negative association with low-fat
dairy intake
High glycaemic load and carbohydrate
intake but not body mass index
Negative association with intake ofsoy products or isoflavones•: description of breast cancer risks is applicable (a blank means not applicable).

to 6.4% (0.7%) at 30–39 years of age, 18.8% (4.5%) at 40–49
years of age, 20.6% (4.6%) at 50–59 years of age and 21.7%(2.4%) at 60–69 years of age. It is worth noting whether
these changes in obesity prevalence will lead to a decline in
the incidence of breast cancer.
To speculate further on the aetiology or modifiable factors
behind the bimodal incidence rates of breast cancer among
Japanese women, recent representative reports on associations
between breast cancer incidence and dietary habits are listed inTable 1, stratified by menopausal status and, if assessed, oestrogen-receptor (OR) expression status. It has been globally

reported that the intake of high-calorie foods, probably relating
to obesity, is associated with the incidence of OR-positive breast
cancer in both pre- and postmenopausal women, while highcarbohydrate or -milk intake that can enhance the secretion of
insulin or insulin-like growth factor 1 is associated with that of
OR-negative breast cancer, mostly in postmenopausal
women.11–15 In a review article,15 it was described that a healthy
dietary pattern to reduce breast cancer risk is characterised by
the high intake of unrefined cereals, vegetables, fruit, nuts andolive oil, and a moderate or low consumption of saturated fatty
acids and red meat. It is of interest that inhibitory effects of soy

4
products or isoflavones on breast cancer incidence have been
observed only in Asian postmenopausal women. Such effects
may also be contributable to suppressing the extent of increasein breast cancer incidence rates among Japanese menopausal
women, leading to the bimodal distribution of age-specificbreast cancer incidence rates.

Conclusions
The age-specific incidence rates of breast cancer among
Japanese women clearly increased from 2000 to 2015 in abimodal distribution pattern, with the conspicuous two peaks.
From the relevant literature, it is inferred that the low prevalence of obesity and intake of soy products or isoflavones
among Japanese women may contribute to the bimodal distribution pattern by suppressing the extent of increase inbreast cancer incidence rates among Japanese postmenopausal women. With regard to dietary habits relating to obesity,
it has been globally reported that high-calorie foods are associated with OR-positive breast cancer in both pre- and postmenopausal women, while high-carbohydrate or -milk intake
that can enhance the secretion of insulin or insulin-like growth
factor 1 is associated with OR-negative breast cancer, mostly
in postmenopausal women. Studies are needed to clarify theaetiology or modifiable factors behind the bimodal incidence
rates of breast cancer among Japanese women.
Acknowledgements
None.

Authors’ contributions
All authors searched the relevant literature, especially on dietary
habits (N.T. and K.M.) and body mass index (R.U.). Y.A. designed thestudy and wrote the manuscript. All authors reviewed and approved
the final version of the manuscript.

Availability of data and materials
Figure 1 was drawn, based on the open data from the website below (inEnglish) of Cancer Information Services, National Cancer Centre, Japan(http://gdb.ganjoho.jp/graph_db/index?changeLang=Submit). Figure 2
was drawn, based on the open data from the website below (in English)of the National Institutes of Health and Nutrition, Japan (Physical Status
Questionnaire, National Health and Nutritional Survey; https://www.
nibiohn.go.jp/eiken/kenkounippon21/en/eiyouchousa/index.html).

Conflict of interest
The authors declared no potential conflicts of interest with respect
to the research, authorship and/or publication of this article.

Ethical approval
Not applicable.

Funding
The authors received no financial support for the research, authorship and/or publication of this article.

Proceedings of Singapore Healthcare﻿Informed consent
Not applicable.

ORCID iD
Yuji Aoki

https://orcid.org/0000-0002-7722-7647

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