Breast Cancer

Bhoo-Pathy et al.
Breast Cancer Research (2015) 17:15

DOI 10.1186/s13058-015-0521-3
RESEARCH ARTICLE
Open Access
Coffee and tea consumption and risk of pre- and

postmenopausal breast cancer in the European
Prospective Investigation into Cancer and
Nutrition (EPIC) cohort study
Nirmala Bhoo-Pathy1,2,3, Petra HM Peeters1,4, Cuno SPM Uiterwaal1, H Bas Bueno-de-Mesquita2,4,5,6, Awang M Bulgiba2,
Bodil Hammer Bech7, Kim Overvad7, Anne Tjnneland8, Anja Olsen8, Franoise Clavel-Chapelon9,10, Guy Fagherazzi9,10,
Florence Perquier9,10, Birgit Teucher11, Rudolf Kaaks11, Madlen Schtze12, Heiner Boeing12, Pagona Lagiou13,
Philippos Orfanos13, Antonia Trichopoulou13,14, Claudia Agnoli15, Amalia Mattiello16, Domenico Palli17,
Rosario Tumino18, Carlotta Sacerdote19, Franzel JB van Duijnhoven5,20, Tonje Braaten21, Eiliv Lund21, Guri Skeie21,
Mara-Luisa Redondo22, Genevieve Buckland23, Maria Jos Snchez Prez24,25, Maria-Dolores Chirlaque25,26,
Eva Ardanaz25,27, Pilar Amiano25,28, Elisabet Wirflt29, Peter Wallstrm29, Ingegerd Johansson30, Lena Maria Nilsson31,
Kay-Tee Khaw32, Nick Wareham33, Naomi E Allen34, Timothy J Key34, Sabina Rinaldi35, Isabelle Romieu35,
Valentina Gallo4,36, Elio Riboli4 and Carla H van Gils1*
Abstract
Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently.
We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer.
Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer
(EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of
breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake
were estimated.
Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were
diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR = 0.90,
95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; Ptrend = 0.029. While there was no significant
effect modification by hormone receptor status (P = 0.711), linear trend for lower risk of breast cancer with increasing
caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast
cancer (P = 0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by
4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal
breast cancer (adjusted HR = 0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose
response relationship (Ptrend = 0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal
breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR = 0.97; 95% CI: 0.82 to 1.14), or to
no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with
premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer.
(Continued on next page)
* Correspondence: c.vangils@umcutrecht.nl
1
Julius Center for Health Sciences and Primary Care, University Medical
Center, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
Full list of author information is available at the end of the article
2015 Bhoo-Pathy et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15
Page 2 of 12
(Continued from previous page)
Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer.
Decaffeinated coffee intake does not seem to be associated with breast cancer.
Introduction
Coffee and tea are the most popular beverages consumed worldwide, rendering them as relevant dietary exposures [1]. Coffee and tea consumption may protect
against breast cancer through anticarcinogenic properties of their biochemical compounds such as caffeine,
polyphenols and diterpenes [2-4] or through favorably
altering the levels of hormones implicated in breast
cancer [5-9]. While polyphenols, including flavonoids,
may mimic estradiol structure and, hence, antagonize
estrogen action, paradoxically, they may also bind weakly
to estrogen receptors and promote estrogen-dependent
transcription [10].
A major systematic review by the World Cancer Research Fund and American Institute for Cancer Research
had concluded that for the association between coffee
and tea intake and pre- and postmenopausal breast cancer, evidence did not allow for definite conclusions [11].
A minority of studies that distinguished between types
of coffee consumed showed contradictory results for decaffeinated coffee [12]. Nevertheless, it is conceivable
that different types of coffee are associated with opposing effects on cancer risk owing to differences in their
constituents. For instance, decaffeinated coffee may contain very low levels of caffeine (up to 0.1%) [13]. Therefore, it is pertinent to further explore the effects arising
from differing caffeine levels in caffeinated and decaffeinated coffee.
Premenopausal and postmenopausal breast cancers
have been argued for some time to be diseases with
somewhat different etiologies [14,15], and it is conceivable that dietary factors may impact the risk of pre- and
postmenopausal breast cancer differently [16]. It has also
been recently hypothesized that breast cancer comprises
two fundamental etiological components, which are to
a certain extent defined by estrogen receptor expression
by age at diagnosis. Therefore, it has been proposed
that in large-scale population based studies, etiological
analyses for breast cancer should be stratified according
to molecular subtypes [17]. To date, relatively few studies have differentiated between pre- and postmenopausal breast cancers [12,18,19] or investigated the
association between coffee and tea intake with breast
cancer based on estrogen receptor (ER) and progesterone receptor (PR) status [12,18,19]. The results have
been overall inconsistent and may be attributed to the
fact that most studies were hampered by limited numbers of cases [12,18,20].
We determined the association between coffee (total,

decaffeinated and caffeinated) and tea consumption with
risk of pre- and postmenopausal breast cancer within
the European Prospective Investigation into Cancer and
Nutrition (EPIC) cohort [21]. Distinction was also made
between breast cancers by hormone receptor status.
Methods
The EPIC study is an on-going multi-center prospective
cohort study aimed at investigating the association between diet, lifestyle, genetic and environmental factors
and the development of cancer and other chronic diseases. It consists of 521,448 men and women, followedup for cancer incidence and cause-specific mortality for
several decades. There are 23 EPIC centers in 10 European
countries, that is, Denmark, France, Germany, Greece,
Italy, Netherlands, Norway, Spain, Sweden, and United
Kingdom. Details have been described elsewhere [21]. At
enrollment between 1992 and 2000, information on habitual diet in the preceding year was collected through a
questionnaire in most countries. Lifestyle questionnaires
were used for information on education, reproductive history, use of oral contraceptives and hormone therapy, family history, medical history, physical activity and history of
consumption of alcohol and tobacco [21].
Study participants
This study pertains to female participants of the EPIC

cohort between 25- and 70-years old at recruitment. We
excluded participants with prior history of cancer, incomplete dietary/non-dietary information, and poorly
completed questionnaires based on their ratio of energy
intake versus energy expenditure (bottom 1% or top 1%
of the cohort), leaving 335,060 women.
All participants provided written informed consent.
The study was approved by the International Agency for
Research on Cancer (IARC)s ethical review committee
and by the respective local ethical committees.
Exposure assessment
Diet was assessed using country-specific questionnaires

[21], namely self-administered semi-quantitative foodfrequency questionnaires (260 food items), dietary history questionnaires (>600 food items) administered by
interviewers, and semi-quantitative food-frequency questionnaires combined with a food record. Further details
on questionnaires and their validation are described
elsewhere [22].
As the exact structure of the questions varied by center and questionnaire, complete information on caffeinated and decaffeinated coffee intake was available only in
Germany, Greece, Italy (except Ragusa and Naples), the
Netherlands, Norway, Spain, Sweden (except Umea), and
the United Kingdom. Analyses of caffeinated and decaffeinated coffee consumption only included women with
complete information on type of coffee intake, that is,
those whose different types of coffee intakes added up to
their total coffee intake. For caffeinated coffee consumption, 226,368 participants were included. Since none of
the participants in Norway and Sweden consumed decaffeinated coffee, they were excluded from analysis for decaffeinated coffee consumption, leaving 176,373 participants.
Information on tea intake was not available in Norway,
leaving 299,890 participants.
As the cohort consists of multiple populations with a
wide range of variation in terms of volume and concentration of coffee and tea intake, country specific quartiles
for these beverages were estimated based on distribution
of intake within each country, after excluding the nonconsumers. This yielded the following intake categories
for total coffee, caffeinated coffee and tea: none, low,
moderately low, moderately high, and high. As decaffeinated coffee intake was less common, we used tertiles of
intake for the consumers and intake categories were:
none, low, medium, and high.
Ascertainment of breast cancer cases
The outcome of interest was first incident of primary invasive breast cancer (coded using International Classification of Diseases for Oncology, Second Edition as
C50.0-C50.9). As data on menopausal status at diagnosis
was lacking, breast cancers occurring before the median
menopausal age of 50 years were considered premenopausal, whereas those diagnosed at 50 years or older
were considered postmenopausal. Information on hormone receptor status was provided by each center based
on pathology reports. This information was routinely
available for tumors diagnosed after 1997 to 2006, depending on the center.
Follow-up
Follow-up was based on linkage with population cancer

registries in Denmark, Italy, Netherlands, Norway, Spain,
Sweden and the United Kingdom. In France, Germany
and Greece, combined methods including health insurance records, cancer and pathology registries, and active
follow-up were used. Censoring dates for most centers
depended on the dates at which cancer registries were
considered complete (varying from December 2004 in
Spain to December 2008 in Italy). In Germany, Greece
and France where active follow-up was undertaken,
dates of censoring were up to March 2010, December
Page 3 of 12
2009, and July 2005, respectively. Loss to follow-up was

less than 4%.
Statistical analysis
Multivariable Cox regression was used to examine the

association between coffee or tea consumption and risk
of breast cancer. Time at entry was age at recruitment,
and exit time was age at diagnosis with breast cancer as
first tumor, death, emigration, loss to follow-up, or end of
follow-up. The non-zero slope of the scaled Schoenfeld
residuals on the time function suggested that the proportional hazard assumption was met. All analyses were
stratified by age at recruitment in one-year categories
and by centers to control for differences in recruitment
or follow-up procedures and questionnaire design. We
studied consumption of beverages both as categorical and
continuous (increment of 100 ml/day) variables. Nonconsumers of coffee comprised a relatively small group
(<10%) and seemed to have some unique health behaviors:
they were less likely to have ever smoked, consume alcohol, or to have ever used oral contraceptives, and they
were more likely to be physically inactive compared to the
rest of the study population. We, therefore, used the low
coffee consumers as the reference group in the categorical
data analysis. To test for linear trends, the categories were
entered as a continuous term (score variable: 0,1,2,3,4) in
the Cox model. Since most coffee consumers tend to consume caffeinated as well as decaffeinated coffee, we additionally cross-classified coffee intakes in relation to breast
cancer. This yielded eight categories, of which (any) decaffeinated coffee consumers with low caffeinated coffee intake comprised the largest group and was hence chosen as
the reference for reasons of statistical robustness.
Two separate Cox models were fitted for pre- and
postmenopausal breast cancers (Additional file 1). Both
models were adjusted for age at menarche (categorical:
<12, 12 to 4, >15 years), ever use of oral contraceptives
(yes/no), age at first delivery (categorical: nulliparous,
<20, 20 to 29, 30 to 39, 40 years), ever breastfeeding
(yes/no), smoking status (categorical: never, past, current),
educational level (categorical: none, primary school, technical/professional school, secondary school, university),
physical activity level based on the Cambridge Physical
Activity Index [23] (categorical: inactive, moderately inactive, moderately active, active), alcohol intake (continuous), height (continuous), weight (continuous), energy
intake from fat source (continuous), energy intake from
non-fat source (continuous), total saturated fat intake
(continuous), and total fiber intake (continuous). The
model for postmenopausal breast cancer was additionally
adjusted for ever-use of postmenopausal hormones (yes/
no). Importantly, coffee and tea intake were mutually adjusted for one another while models for caffeinated and
decaffeinated coffee were also mutually adjusted.
As data on hormone receptor status was only available

in breast cancer cases diagnosed after 1997 to 2006, depending on the center, it is mainly the postmenopausal
cases that had receptor status available (77.2%) and only
about half of the premenopausal cases (58.6%). Hormonereceptor defined analyses were, hence, only done among
postmenopausal breast cancers and were not possible
within premenopausal breast cancers.
As a form of sensitivity analysis, we also analyzed beverage intake using categories based on the overall cohort
instead of country specific intake.
To improve comparability across centers, dietary intake was calibrated by a 24-hour dietary recall method
common to all centers, in a random sub-sample of 8% of
the cohort at baseline (Additional file 1) [24,25].
Heterogeneity of the association according to hormone
receptor status was assessed using a data-augmentation
method described by Lunn and McNeil [26]. Effect
modification by body mass index [27] and country were
assessed, and several sensitivity analyses were conducted
(Additional file 1).
Two-tailed P-values <0.05 and 95% confidence intervals (CI) for hazard ratios (HRs) not including 1 were
considered statistically significant. All analyses were performed using SAS version 9.1 (SAS Institute Inc, Cary,
NC, USA).
Results
A great majority of the study participants consumed coffee, with a median total coffee intake ranging from
93 ml/day in Italy to 900 ml/day in Denmark (not
shown). Decaffeinated coffee was consumed by about
50% of the study population. Median decaffeinated coffee intake ranged from 2 ml/day in Spain and United
Kingdom to 140 ml/day in France. Tea was consumed
by approximately 66% of the total cohort resulting in a
median intake ranging from close to 0 ml/day in Greece
to up to 475 ml/day in United Kingdom.
The mean age at recruitment was 51 years with 43% of
the participants being postmenopausal. Based on body
mass index (BMI) classification by the World Health
Organization, 58% of participants were of normal weight,
29% overweight and 13% obese.
Compared to the low coffee consumers, those with
high coffee consumption were more likely to have ever
smoked, used oral contraceptives, be physically active,
and consumed more alcohol but less tea (Table 1). They
were also more likely to comprise women attaining early
menarche, and those with very young age at first childbirth (<20 years). In contrast, participants with high decaffeinated coffee intake were less likely to have used
oral contraceptives, and more likely to be postmenopausal, and use hormone replacement therapy, compared to the low consumers. They also less frequently
Page 4 of 12
attained tertiary education, and were more likely to have

breastfed their offspring. However, compared to nonconsumers, consumers of (any) decaffeinated coffee were
more likely to have attained tertiary education, be physically active, be non-smokers, and less likely to be very
young at first childbirth (not shown). Compared to low
tea intake, those with high tea intake were more likely to
be older at recruitment, have higher education status, be
more active physically, use more oral contraceptives, be
older at first delivery, be postmenopausal, and use hormone replacement therapy.
During an average 11 years of follow-up, 10,198 first
incidences of primary invasive breast cancer were observed among 335,060 women. Of these, 1,064 were premenopausal breast cancers. Hormone receptor status
was available in approximately 70% (7,053) of total
breast cancer cases, out of which 50% were double hormone receptor positive tumors (ER+ PR+), followed by
33% of single hormone receptor positive tumors (ER+ or
PR+), whereas 17% were double negative tumors (ER- PR-).
Tables 2, 3, 4, 5 and 6 show the numbers of participants, cases, and multivariable adjusted HRs for each
category of coffee (total, caffeinated, decaffeinated intake) and tea intake. For analysis of beverages as continuous value (per 100 ml increment), the observed and
calibrated HRs were identical. We only present the observed HR.
Total coffee
While moderately low intake of total coffee consumption

seemed to be associated with higher risk of premenopausal breast cancer (adjusted HR:1.23, 95% CI: 1.02 to
1.48, compared to low intake), no dose response relationship was observed; Ptrend = 0.272 (Table 2). Overall,
intake of total coffee was associated with a borderline
statistically significantly lower risk of postmenopausal
breast cancer. Multivariable HR comparing high total
coffee intake to low intake was 0.95 (95% CI: 0.89 to
1.01). The linear trend test was not significant; Ptrend =
0.055. Each 100 ml increase in daily intake of total coffee
was inversely associated with breast cancer risk (HR
continuous 0.99, 95% CI: 0.98 to 0.99).
Caffeinated coffee
There seemed to be no association between caffeinated

coffee intake and premenopausal breast cancer (Table 3).
However, higher intakes of caffeinated coffee were associated with lower risk of postmenopausal breast cancer
(adjusted HR for high intake compared to low intake:
0.90; 95% CI: 0.82 to 0.98). A linear trend for the inverse
associations of caffeinated coffee intake with postmenopausal breast cancer risk was also apparent in this analysis;
Ptrend = 0.029 (Table 3). While there was no significant effect modification by hormone receptor status (P = 0.711),
Page 5 of 12
Table 1 Distribution of risk factors according to levels of consumption of coffee (total, caffeinated and decaffeinated)
and tea
Total
Age at recruitment (mean (years))

g
51
Coffee (total)a
Coffee caffeinatedb
Coffee decaffeinatedc
Tead
Low
intakee
High
intakee
Low
intakee
High
intakee
Low
intakef
High
intakef
Low
intakee
High
intakee
51
50
49
50
47
50
49
52
Familial breast cancer (%)
8.3
8.6
7.9
9.5
9.0
10.6
9.9
9.6
9.3
Age at menarche (% <12 years)
15.0
13.6
17.1
13.3
15.6
16.5
17.5
15.8
14.7
Oral contraceptive use (% ever)
58.7
58.1
61.3
65.2
68.4
71.5
67.8
62.6
67.1
Nulliparity (%)
4.1
5.3
4.1
6.8
4.6
6.2
3.7
4.0
3.0
Age at first delivery (% < 20 years)h
14.8
13.4
18.1
13.2
18.0
10.1
11.1
15.2
12.3
Breastfed offsprings (% ever)
72.2
71.1
72.4
73.7
74.9
60.7
66.7
66.3
68.5
Postmenopausal (%)
43.4
43.1
38.5
38.6
38.5
34.9
42.0
40.4
45.7
Menopausal hormone use (% ever)
26.0
25.7
25.6
26.9
28.5
19.5
24.0
23.2
31.6
Education (% university)
23.6
25.1
22.7
28.6
23.4
37.6
29.1
33.2
37.7
Smokers (% ever)
42.0
35.6
54.6
40.5
57.6
40.3
43.6
43.5
42.1
Physically inactivei (%)
24.3
25.6
22.8
19.3
19.1
19.4
18.9
21.2
16.4
BMI (mean (kg/m2))
25.0
24.8
25.2
24.2
24.9
24.2
24.9
24.8
24.1
Alcohol intake (median (g/day))
3.6
2.9
4.2
3.2
4.7
4.5
4.0
4.2
5.2
Energy intake (mean (kcal/day))
1931
1863
2008
1835
1968
1892
1919
1906
2003
Fat intake (mean (g/day))
25
24
26
23
24
22
22
25
23
Fruits intake (mean (g/day))
250
249
245
232
216
254
261
255
244
Vegetable intake (mean (g/day))
219
214
227
204
196
238
236
231
227
Tead intake (median (ml/day))
29
14
15
356
238
12
814
Coffeej intake (median (ml/day))
290
70
750
190
81
376
150
Includes all 335,060 participants. bIncludes 226,368 participants with complete data on type of coffee intake, that is, France (n = 48,101), Germany (n = 27,411),
Greece (n = 3,125), Italy (n = 11,737), Netherlands (n = 26,866), Norway (n = 35,170), Spain (n = 6,589), Sweden (n = 14,825), and United Kingdom (n = 52,544).
c
Includes 176,373 participants with complete data on type of coffee intake, that is, France (n = 48,101), Germany (n = 27,411), Greece (n = 3,125), Italy (n = 11,737),
Netherlands (n = 26,866), Spain (n = 6,589), and United Kingdom (52,544). Participants from Norway and Sweden are all non-consumers of decaffeinated coffee
and were excluded. dIncludes 299,890 participants. Participants from Norway were excluded as their information on tea intake is not available. eCut-off points are
based on country specific quartiles of beverage intake after exclusion of non-consumers; low: quartile 1, high: quartile 4. fCut-off points are based on country
specific tertiles of decaffeinated coffee intake after exclusion of non-consumers; low: tertile 1, high: tertile 3. gIn first degree relative (available for 43% of women).
h
Only for parous women. iUsing Cambridge Physical Activity Index. jFor caffeinated coffee categories, median decaffeinated coffee intake is given and vice versa.
a linear trend for lower risk of breast cancer with increasing

caffeinated coffee intake was clearest for ER- PR- breast
cancer (P = 0.008). For every 100 ml higher caffeinated
coffee consumption, the risk of ER- PR- breast cancer was
lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). The
risk of ER+ PR+ breast cancer was lowered by 2% per
100 ml (adjusted HR: 0.98, 95% CI: 0.96 to 0.99). However,
the P value for trend test of categorical analyses was not
significant (Table 3).
Decaffeinated coffee
No association was observed between decaffeinated coffee intake and premenopausal breast cancer (Table 4).
Non-consumers compared to low consumers of decaffeinated coffee did show a significantly lower postmenopausal breast cancer risk (adjusted HR: 0.89; 95% CI:
0.80 to 0.99). There was, however, no difference in risk
of breast cancer between high decaffeinated coffee consumers, compared to low consumers (Table 4). Post-hoc
analysis comparing non-consumers of decaffeinated coffee against the consumers (no intake versus any intake,
irrespective of caffeinated coffee intake) showed a modest decrease in risk of postmenopausal breast cancer; adjusted HR: 0.90, 95% CI: 0.82 to 0.98. There was no dose
response relationship (Ptrend = 0.128).
Compared to low decaffeinated coffee consumers, it
seemed that the non-consumers of decaffeinated coffee
had a lower risk of developing ER- PR- breast cancer
(adjusted HR:0.69, 95% CI: 0.50 to 0.94), than ER+ PR+
breast cancer (adjusted HR: 0.88, 95% CI:0.73 to 1.05).
However, test for interaction with hormone receptor status was not statistically significant (P = 0.716).
Cross-classification of caffeinated and decaffeinated coffee
As compared to decaffeinated coffee consumers with

low caffeinated coffee intake, non-consumers of decaffeinated coffee with higher intakes of caffeinated coffee
had significantly lower risk of postmenopausal breast
Page 6 of 12
Table 2 Total coffee consumption and risk of breast cancera

Daily coffee intake
Total
No intake
Low
intakeb
Moderately
low intakeb
Moderately
high intakeb
High
intakeb
Number of participants
335060
26734
87501
71684
79838
69303
Ptrendc
Per 100 mls
0.272
1.00 (0.98-1.03)
0.055
0.99 (0.98-0.99)
0.187
0.99 (0.97-1.00)
Number of breast cancers
10198
813
2542
2213
2518
2112
Premenopausal breast cancers
1064
81
246
234
251
252
1.08 (0.83-1.40)
1.00
1.23 (1.02-1.48)
1.11 (0.93-1.34)
1.15 (0.96-1.39)
732
2296
1979
2267
1860
1.02 (0.94-1.12)
1.00
0.97 (0.91-1.03)
0.97 (0.92-1.03)
0.95 (0.89-1.01)
285
860
670
776
615
0.97 (0.84-1.11)
1.00
0.96 (0.86-1.06)
0.98 (0.88-1.08)
0.91 (0.81-1.01)
93
269
222
257
211
0.99 (0.78-1.26)
1.00
0.84 (0.70-1.01)
0.89 (0.74-1.06)
0.86 (0.71-1.05)
0.135
0.99 (0.97-1.01)
Adjusted Hazard Ratio (95% CI)h
0.99 (0.76-1.29)
1.00
1.01 (0.84-1.20)
1.01 (0.83-1.83)
1.09 (0.88-1.35)
0.501
1.00 (0.98-1.03)
Adjusted Hazard Ratio (95% CI)i
1.03 (0.94-1.13)
1.00
0.99 (0.92-1.06)
0.98 (0.91-1.05)
0.95 (0.88-1.02)
0.067
0.99 (0.98-0.99)
Adjusted Hazard Ratio (95% CI)d

Postmenopausal breast cancers
9134
Adjusted Hazard Ratio (95% CI)e

ER+ and PR+ breast cancers
3206
Adjusted Hazard Ratio (95% CI)f

ER- and PR- breast cancers
1052
Adjusted Hazard Ratio (95% CI)g

Analysis by cohort-wide intake
Includes all 335,060 participants. Cut-off points are based on country specific quartiles of total coffee intake after exclusion of non-coffee consumers. cP for trend
is computed by entering the categories as a continuous term (score variable: 0,1,2,3,4) in the Cox model. dIncluding only premenopausal breast cancers (that is,
breast cancer diagnosed before the age of 50 years), and participants who were premenopausal at recruitment. Model is stratified by study center and age at
recruitment, and adjusted for age at menarche, ever use of oral contraceptives, age at first delivery, breastfeeding, smoking, education, physical activity level,
alcohol intake, height, weight, energy intake from fat sources, energy intake from non-fat sources, saturated fat intake, fruits and vegetable intake, and tea intake.
e
Including only postmenopausal breast cancers (excluding participants with premenopausal breast cancers). Model is stratified by study center and age at recruitment,
and adjusted for age at menarche, ever use of oral contraceptives, age at first delivery, breastfeeding, menopausal status at recruitment, ever use of postmenopausal
hormones, smoking, education, physical activity level, alcohol intake, height, weight, energy intake from fat sources, energy intake from non-fat sources, saturated fat
intake, fruits and vegetable intake, and tea intake. fHormone receptor status was only known in approximately 67% of patients with breast cancer. This analysis includes
only estrogen receptor positive and progesterone receptor positive postmenopausal breast cancers, fully adjusted as in model 5. gHormone receptor status was only
known in approximately 67% of patients with breast cancer. This analysis includes only estrogen receptor negative and progesterone receptor negative postmenopausal
breast cancers, fully adjusted as in model 5. hIncluding only premenopausal breast cancers. Using total coffee intake in cohort wide categories (no intake, quartile 1,
quartile 2, quartile 3, quartile 4), and fully adjusted as in model 4. iIncluding only postmenopausal breast cancers. Using total coffee intake in cohort wide categories (no
intake, quartile 1, quartile 2, quartile 3, quartile 4), and fully adjusted as in model 5. CI, confidence interval; ER, estrogen receptor; PR, progesterone receptor.
a
cancer. Within consumers of decaffeinated coffee, no

such association with higher intakes of caffeinated coffee
was observed. Exclusive decaffeinated coffee consumption was also not associated with risk of postmenopausal
breast cancer compared to decaffeinated coffee consumption with low caffeinated coffee intake (Table 5).
Post-hoc analysis within women who did not consume any
caffeinated coffee, showed no difference in risk of postmenopausal breast cancer between 21,239 non-consumers
of decaffeinated coffee and 9,810 decaffeinated coffee consumers (adjusted HR: 0.96; 95%: 0.82 to 1.14).
was conducted using cohort wide categories of intake instead of country specific categories (Tables 2, 3, 4 and 6).
We did not observe any effect modification by BMI. There
was no statistically significant heterogeneity between
countries for the association between total coffee, caffeinated coffee, decaffeinated coffee, and tea intake and breast
cancer. None of the associations were substantially altered
when family history of breast cancer was included in the
analyses, or when analysis was restricted to follow-up experience after two years of recruitment into the study (not
shown).
Tea
Discussion
In this study, high versus low caffeinated coffee intake was
associated with a modest but statistically significantly
lower risk of postmenopausal breast cancer. This association was only detected in women not consuming decaffeinated coffee. Although abstinence of decaffeinated
coffee (versus any intake, irrespective of caffeinated coffee
intake) seemed to be associated with lower risk for postmenopausal breast cancer, exclusive decaffeinated coffee
intake was not associated with increased risk. Tea intake
was not associated with risk of postmenopausal breast cancer. Neither caffeinated coffee, decaffeinated coffee, nor tea
intake impacted the risk of premenopausal breast cancer.
Tea consumption was neither statistically significantly

associated with risk of premenopausal nor postmenopausal breast cancer (Table 6). The adjusted HR for high
tea intake versus low intake was 0.98 (95% CI: 0.77 to
1.26) for premenopausal breast cancer, and 0.95 (95%
CI: 0.88 to 1.03) for postmenopausal breast cancer. Analysis by hormone receptor status did not show any significant results.
Sensitivity analysis
Our sensitivity analyses showed that results remain essentially unchanged when analysis of beverage intake
Page 7 of 12
Table 3 Caffeinated coffee consumption and risk of breast cancera

Total
No. of participants
226 368
35590
60772
46429
43565
40012
No. of breast cancers
6794
1068
1783
1360
1356
1227
724

Postmenopausal cancers
6070

ER+ and PR+ subtype
2142

ER- and PR- subtype
605
No intake of
caffeinated
coffee
Low
intakeb
Moderately
low intakeb
Moderately
high intakeb
High intakeb
Daily caffeinated coffee intake
Ptrendc
Per 100 mls
0.547
1.00 (0.97-1.03)
0.029
0.98 (0.97-1.00)
0.140
0.98 (0.96-0.99)
102
189
159
133
141
1.14 (0.86-1.53)
1.00
1.23 (0.97-1.55)
1.01 (0.79-1.28)
1.19 (0.93-1.53)
966
1594
1201
1223
1086
1.00 (0.91-1.09)
1.00
0.89 (0.82-0.97)
0.97 (0.90-1.05)
0.90 (0.82-0.98)
386
602
363
416
375
0.93 (0.80-1.08)
1.00
0.85 (0.74-0.98)
0.96 (0.84-1.10)
0.84 (0.73-0.97)
126
154
116
104
105
1.14 (0.88-1.48)
1.00
0.89 (0.69-1.16)
0.81 (0.62-1.05)
0.80 (0.61-1.05)
0.008
0.96 (0.93-1.00)
1.12 (0.83-1.51)
1.00
1.17 (0.92-1.47)
0.97 (0.75-1.26)
1.11 (0.84-1.48)
0.989
1.00 (0.97-1.03)
1.01 (0.92-1.12)
1.00
0.96 (0.88-1.04)
0.97 (0.89-1.06)
0.91 (0.83-1.00)
0.051
0.98 (0.97-1.00)

i
Adjusted Hazard Ratio (95% CI)

a
Netherlands (n = 26,866), Norway (n = 35,170), Spain (n = 6,589), Sweden (n = 14,825), and United Kingdom (n = 52,544). bCut-off points are based on country
specific quartiles of caffeinated coffee intake after exclusion of non-caffeinated coffee consumers. cP for trend is computed by entering the categories as a
continuous term (score variable: 0,1,2,3,4) in the Cox model. dIncluding only premenopausal breast cancers (that is, breast cancer diagnosed before the age of
50 years), and participants who were premenopausal at recruitment. Model is stratified by study center and age at recruitment, and adjusted for age at menarche,
ever use of oral contraceptives, age at first delivery, breastfeeding, smoking, education, physical activity level, alcohol intake, height, weight, energy intake from
fat sources, energy intake from non-fat sources, saturated fat intake, fruits and vegetable intake, decaffeinated coffee intake, and tea intake. eIncluding only
postmenopausal breast cancers (excluding participants with premenopausal breast cancers). Model is stratified by study center and age at recruitment, and
adjusted for age at menarche, ever use of oral contraceptives, age at first delivery, breastfeeding, menopausal status at recruitment, ever use of postmenopausal
hormones, smoking, education, physical activity level, alcohol intake, height, weight, energy intake from fat sources, energy intake from non-fat sources, saturated
fat intake, fruits and vegetable intake, decaffeinated coffee intake, and tea intake. fHormone receptor status was only known in approximately 67% of patients
with breast cancer. This analysis includes only estrogen receptor positive and progesterone receptor positive postmenopausal breast cancers, fully adjusted as in
model 5. gHormone receptor status was only known in approximately 67% of patients with breast cancer. This analysis includes only estrogen receptor negative
and progesterone receptor negative postmenopausal breast cancers, fully adjusted as in model 5. hIncluding only premenopausal breast cancers. Using caffeinated
coffee intake in cohort wide categories (no intake, quartile 1, quartile 2, quartile 3, quartile 4), and fully adjusted as in model 4. iIncluding only postmenopausal
breast cancers. Using caffeinated coffee intake in cohort wide categories (no intake, quartile 1, quartile 2, quartile 3, quartile 4), and fully adjusted as in model 5.
CI, confidence interval, ER, estrogen receptor; PR, progesterone receptor.
Our null finding for the association between total coffee intake and risk of postmenopausal breast cancer corroborates the findings of most previous large-scale
prospective studies and meta-analyses [12,28]. The lack
of association observed in the current study and previous studies seems to support the notion that studying
total coffee intake as a single entity may result in a net
null association owing to differences in the direction of
association between caffeinated and decaffeinated coffee,
in relation to breast cancer. Hence, we would like to recommend that future studies in populations consuming
both types of coffee should explicitly analyze caffeinated
and decaffeinated coffee intake separately.
The observation that caffeinated coffee was significantly associated with lower risk of postmenopausal
breast cancer seems to be in agreement with the finding
of a recent population based casecontrol study by
Lowcock et al. in Canada (odds ratio comparing highest
versus no consumption: 0.63 (95% CI: 0.43 to 0.94) [19].
This study, and another population-based casecontrol
study, which included participants from Sweden as well
as Germany [29], had further found that caffeinated coffee intake was significantly associated with a reduced
risk of estrogen receptor negative breast cancers but not
estrogen receptor positive breast cancers, while we
found a stronger association in ER- PR- breast cancers.
A cohort study in Sweden had also found that increased
coffee intake was associated with lower risk of ER- PRbreast cancer, but at a more modest margin of protection,
not achieving statistical significance [30]. Other recent
prospective cohort studies, however, could not show an
association between caffeinated coffee intake and risk of
breast cancer [31-35]. While it seems plausible that caffeine plays a role in explaining the lower risk of breast
cancer associated with caffeinated coffee intake in the
current study [35], a number of studies have shown that
caffeine intake per se does not impact breast cancer risk
[19,32-34,36]. It is hence postulated that another compound, or compounds, in caffeinated coffee may confer a
protection against breast carcinogenesis by acting synergistically with caffeine [19]. This explanation seems plausible given that in our study, caffeinated coffee, which
Page 8 of 12
Table 4 Decaffeinated coffee consumption and risk of breast cancera

Daily decaffeinated coffee intake
Total
No intake of
decaffeinated
coffee
Low intakeb
Moderate intakeb
High intakeb
No. of participants
176373
88868
43173
16798
27534
No. of breast cancers
5272
2858
1088
515
811
587

4685

ER+ and PR+ subtype
1749

ER- and PR- subtype
512
Ptrendc
Per 100 mls
0.646
1.00 (0.94-1.06)
0.128
1.01 (0.99-1.03)
0.036
1.02 (0.99-1.06)
289
149
48
101
1.08 (0.79-1.49)
1.00
0.86 (0.56-1.32)
1.20 (0.90-1.60)
2569
939
467
710
0.89 (0.80-0.99)
1.00
1.01 (0.89-1.15)
0.97 (0.87-1.08)
1073
280
174
222
0.88 (0.73-1.05)
1.00
0.98 (0.79-1.21)
1.07 (0.89-1.30)
304
93
51
64
0.69 (0.50-0.94)
1.00
0.92 (0.63-1.34)
0.72 (0.51-1.02)
0.705
0.97 (0.91-1.04)
1.08 (0.76-1.53)
1.00
0.88 (0.62-1.27)
1.16 (0.84-1.60)
0.915
1.00 (0.94-1.06)
0.87 (0.75-1.01)
1.00
1.00 (0.86-1.16)
0.95 (0.83-1.10)
0.081
1.01 (0.99-1.03)

i
Adjusted Hazard Ratio (95% CI)

a
Netherlands (n = 26,866), Spain (n = 6,589), and United Kingdom (52,544). Participants from Norway and Sweden are all non-consumers of decaffeinated coffee
and were excluded. bCut-off points are based on country specific tertiles of decaffeinated coffee intake after exclusion of non-decaffeinated coffee consumers.
c
P for trend is computed by entering the categories as a continuous term (score variable: 0,1,2,3,4) in the Cox model. dIncluding only premenopausal breast
cancers (that is, breast cancer diagnosed before the age of 50 years), and participants who were premenopausal at recruitment. Model is stratified by study center
and age at recruitment, and adjusted for age at menarche, ever use of oral contraceptives, age at first delivery, breastfeeding, smoking, education, physical activity
level, alcohol intake, height, weight, energy intake from fat sources, energy intake from non-fat sources, saturated fat intake, fruits and vegetable intake, caffeinated
coffee intake, and tea intake. eIncluding only postmenopausal breast cancers (excluding participants with premenopausal breast cancers). Model is stratified by study
center and age at recruitment, and adjusted for age at menarche, ever use of oral contraceptives, age at first delivery, breastfeeding, menopausal status at recruitment,
ever use of postmenopausal hormones, smoking, education, physical activity level, alcohol intake, height, weight, energy intake from fat sources, energy intake from
non-fat sources, saturated fat intake, fruits and vegetable intake, caffeinated coffee intake, and tea intake. fHormone receptor status was only known in approximately
67% of patients with breast cancer. This analysis includes only estrogen receptor positive and progesterone receptor positive postmenopausal breast cancers, fully
adjusted as in model 5. gHormone receptor status was only known in approximately 67% of patients with breast cancer. This analysis includes only estrogen receptor
negative and progesterone receptor negative postmenopausal breast cancers, fully adjusted as in model 5. hIncluding only premenopausal breast cancers. Using
caffeinated coffee intake in cohort wide categories (no intake, quartile 1, quartile 2, quartile 3, quartile 4), and fully adjusted as in model 4. iIncluding only
postmenopausal breast cancers. Using caffeinated coffee intake in cohort wide categories (no intake, quartile 1, quartile 2, quartile 3, quartile 4), and fully adjusted as in
model 5. CI, confidence interval, ER, estrogen receptor; PR, progesterone receptor.
Table 5 Cross-classified coffee intake and risk of postmenopausal breast cancera

Decaffeinated coffee
Caffeinated coffee
No consumption
No consumption
Consumption
568/21239
287/9810
Adjusted hazard ratio (95%CI)
0.89 (0.77-1.04)
0.97 (0.82-1.14)
Number of postmenopausal breast cancers/Number of participants
625/20480
601/29716
0.88 (0.77-1.02)
1.00
836/27498
588/22347
0.84 (0.74-0.97)
0.95 (0.83-1.08)
540 19561
630/25632
0.82 (0.71-0.95)
0.98 (0.87-1.11)

c
Low consumptionb
Moderate consumptionb
High consumptionb

a
Netherlands (n = 26,866), Spain (n = 6,589), and United Kingdom (52,544). Participants from Norway and Sweden are all non- consumers of decaffeinated coffee
and were excluded. bThe cut-off values are based on country specific tertiles. cIncludes only postmenopausal breast cancers. Model is stratified by study center
and age at recruitment, and adjusted for age at menarche, ever use of oral contraceptives, age at first delivery, breastfeeding, menopausal status, ever use of
postmenopausal hormones, smoking, education, physical activity level, alcohol intake, height, weight, energy intake from fat sources, energy intake from non-fat
sources, saturated fat intake, fruits and vegetable intake, and tea intake. CI, confidence interval.
Page 9 of 12
Table 6 Tea consumption and risk of breast cancera

Ptrendc
Per 100 mls
0.624
1.00 (0.98-1.03)
0.375
1.00 (0.99-1.00)
0.866
1.00 (0.99-1.02)
1.12 (0.89-1.42)
0.941
1.00 (0.98-1.02)
0.94 (0.75-1.17)
0.97 (0.75-1.25)
0.770
1.00 (0.98-1.03)
1.01 (0.93-1.10)
0.99 (0.91-1.08)
0.998
1.00 (0.99-1.00)
Daily tea intake
Total
No intake
Low
intakeb
Moderately
low intakeb
Moderately
high intakeb
High intakeb
Number of participants
299890
99667
58966
54485
52280
34492
Number of breast cancers
9344
3043
1704
1738
1680
1179
0.90 (0.73-1.12)
1.00
0.98 (0.80-1.21)
0.97 (0.79-1.20)
0.98 (0.77-1.26)
2771
1486
1566
1510
1074
0.99 (0.92-1.06)
1.00
1.00 (0.93-1.08)
0.98 (0.91-1.06)
0.95 (0.88-1.03)
903
496
477
543
398
1.03 (0.91-1.15)
1.00
0.98 (0.86-1.11)
1.05 (0.93-1.19)
1.02 (0.89-1.17)
268
177
182
180
152
1.12 (0.91-1.38)
1.00
0.99 (0.80-1.22)
1.03 (0.83-1.27)
0.91 (0.74-1.13)
1.00
1.04 (0.85-1.27)
Adjusted Hazard Ratio (95% CI)i
1.01 (0.93-1.09)
1.00
1.01 (0.94-1.10)

8407

ER+ and PR+ subtype
2817

ER- and PR- subtype
959
Includes 299890 participants, following exclusion of participants from Norway where data on tea intake is not available. Cut-off points are based on country
specific quartiles of tea intake after exclusion of non-tea consumers. cP for trend is computed by entering the categories as a continuous term (score variable:
0,1,2,3,4) in the Cox model. dIncluding only premenopausal breast cancers (that is, breast cancer diagnosed before the age of 50 years), and participants who were
premenopausal at recruitment. Model is stratified by study center and age at recruitment, and adjusted for age at menarche, ever use of oral contraceptives, age
at first delivery, breastfeeding, smoking, education, physical activity level, alcohol intake, height, weight, energy intake from fat sources, energy intake from
non-fat sources, saturated fat intake, fruits and vegetable intake, coffee intake. eIncluding only postmenopausal breast cancers (excluding participants with
premenopausal breast cancers). Model is stratified by study center and age at recruitment, and adjusted for age at menarche, ever use of oral contraceptives, age
at first delivery, breastfeeding, menopausal status at recruitment, ever use of postmenopausal hormones, smoking, education, physical activity level, alcohol intake,
height, weight, energy intake from fat sources, energy intake from non-fat sources, saturated fat intake, fruits and vegetable intake, coffee intake. fHormone
receptor status was only known in approximately 67% of patients with breast cancer. This analysis includes only estrogen receptor positive and progesterone
receptor positive postmenopausal breast cancers, fully adjusted as in model 5. gHormone receptor status was only known in approximately 67% of patients with
breast cancer. This analysis includes only estrogen receptor negative and progesterone receptor negative postmenopausal breast cancers, fully adjusted as in
model 5. hIncluding only premenopausal breast cancers. Using tea intake in cohort wide categories (no intake, quartile 1, quartile 2, quartile 3, quartile 4), and fully
adjusted as in model 4. iIncluding only postmenopausal breast cancers. Using tea intake in cohort wide categories (no intake, quartile 1, quartile 2, quartile 3,
quartile 4), and fully adjusted as in model 5. CI, confidence interval, ER, estrogen receptor; PR, progesterone receptor.
contains caffeine and a plethora of other compounds, was

associated with lower risk of postmenopausal breast cancer, whereas decaffeinated coffee does not seem to be associated with risk of breast cancer.
In this study, those who reported not to consume decaffeinated coffee seemed to have a significantly lower
risk of breast cancer. However, we did not observe a
doseresponse relationship. Cross-classified coffee intake analysis further showed that exclusive decaffeinated
coffee consumption was not associated with risk of postmenopausal breast cancer compared to decaffeinated
coffee and low caffeinated coffee consumption. Post-hoc
analyses also showed that exclusive decaffeinated coffee
consumption was not associated with increased risk of
postmenopausal breast cancer compared to no intake of
any coffee. Taken together, these findings seem to suggest that decaffeinated coffee intake is not associated
with postmenopausal breast cancer. The apparent decrease in risk among non-consumers of decaffeinated
coffee may be explained by findings of previous studies,
which have suggested that decaffeinated coffee consumers may be unique in terms of lifestyle or medical
history [37,38]. Decaffeinated coffee intake is related to
illness in some persons but to a healthy lifestyle in others

[37]. This is corroborated in the current study, where consumption of decaffeinated coffee was associated with a
healthier lifestyle compared to non-consumption. Hence,
there may have been minimal overlap in (lifestyle related)
confounders between the consumers and non-consumers
of decaffeinated coffee to allow optimal adjustment. It is
also conceivable that the breast cancer screening behavior
of decaffeinated coffee consumers may have contributed
to higher detection of (early) breast cancers in this subgroup. This may also explain why higher caffeinated coffee
intakes within decaffeinated coffee consumers were not
associated with a lower risk of breast cancer. It is, however, acknowledged that distinguishing genuine decaffeinated coffee effects from a decaffeinated coffee preference
effect may be difficult.
A meta-analysis on the association of tea intake with
breast cancer risk had found no overall protective effect
of black tea (pooled relative risk = 0.97; 95% CI = 0.91 to
1.05) [3]. This corroborates our findings since black tea
is the predominantly consumed type of tea in Europe
[39]. Possibly explaining the lack of association between
black tea and breast cancer is that it contains a relatively
lower amount of caffeine compared to coffee, and up to

10-fold reduction in catechin levels compared with
green tea, which had been inversely associated with
breast cancer [39].
Besides having a sufficiently large number of premenopausal breast cancers, we also had a relatively high number of breast cancer cases whose hormone receptor
statuses were available (approximately 70%) to allow
analysis by ER and PR status. Our findings further support the view that pooling of pre- and postmenopausal
breast cancers as a homogenous entity is not recommended. We do, however, acknowledge that data on
menopausal status at diagnosis was not available, and we
had to use age at breast cancer diagnosis as a proxy. Although coffee and tea intakes were measured only at
baseline, analyses of participants in the EPIC sub-cohort
of Umea in Sweden [40], as well as participants of the
Cancer Prevention Study II in the United States [41],
with repeated measures taken up to 10 years apart
showed that coffee habits are stable over a long period.
While the amount of coffee intake seems to vary substantially across Europe, true variation in coffee intake
may not be as large as it seems given that there is an inverse relationship between the volume and concentration of coffee. This is reflected in our results whereby
the hazard ratios using cohort-wide cutpoints are similar
to country-specific cutpoints. We did not have information on the type of tea, and coffee/tea brewing methods,
which may vary across the countries and alter the contents of potentially beneficial compounds in the beverages. It has been recently highlighted that coffee brewing
methods maybe be relevant with respect to breast cancer
risk. A cohort study in Sweden showed that a decreased
risk of breast cancer was observed in women drinking
boiled coffee but no association was observed with filtered coffee consumption [42]. Country specific categories of consumption were therefore used to address this
limitation. Besides coffee and tea as prominent sources of
caffeine in this population, hot chocolate, chocolate
candy/candy bars, and soft drinks are also possible
sources [43]. We had information on chocolate candy/
candy bars intake and soft drinks, but not on hot chocolate intake. As contributions of caffeine from these
sources are far lower than from coffee and tea, those intakes are unlikely to have impacted our study results [43].
Conclusions
Within a very large cohort of women, our findings show
that higher caffeinated coffee intake is associated with a
modest lowering in risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with risk of breast cancer. The mechanism by
which caffeinated coffee impacts breast cancer risk warrants further investigation.
Page 10 of 12
Additional file
Additional file 1: Supplementary methods. Cox regression models for
pre- and postmenopausal breast cancers.
Abbreviations
BMI: body mass index; CI: confidence interval; EPIC: European Prospective
Investigation into Nutrition and Cancer; ER: estrogen receptor; HR: hazard
ratio; IARC: International Agency for Research on Cancer; PR: progesterone
receptor.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
NB, CVG, CSPMU, and PHMP designed the study. NB, PHMP, CSPMU, HBB,
AMB, BHB, KO, AT, AO, FC, GF, FP, BT, RK, MS, HB, PL, PO, A Trichopoulou, CA,
AM, DP, RT, CS, FJBVD, TB, EL, GS, MR, GB, MJSP, MC, EA, PA, EW, PW, IJ, LMN,
KK, NW, NEA, TJK, SR, IR, VG, ER, and CVG collected data, and provided
administrative, technical or material support. NB, CVG, CSPMU, HBB, and
PHMP did the statistical analyses, and interpreted the data. Drafting of the
manuscript was done by NB, CVG, CSPMU, HBB, and PHMP. NB, PHMP,
CSPMU, HBB, AMB, BHB, KO, AT, AO, FC, GF, FP, BT, RK, MS, HB, PL, PO, A
Trichopoulou, CA, AM, DP, RT, CS, FJBVD, TB, EL, GS, MR, GB, MJSP, MC, EA,
PA, EW, PW, IJ, LMN, KK, NW, NEA, TJK, SR, IR, VG, ER, and CVG critically
reviewed the manuscript for important intellectual content. All authors read
and approved the final manuscript.
Acknowledgements
This work was supported by the European Commission (DG-SANCO) and the
International Agency for Research on Cancer. The national cohorts are
supported by Danish Cancer Society (Denmark); Ligue contre le Cancer, 3 M,
Mutuelle Gnrale de lEducation Nationale, Institut National de la Sant et
de la Recherche Medicale (France); Deutsche Krebshilfe, Deutsches
Krebsforschungszentrum and Federal Ministry of Education and Research
(Germany); Hellenic Health Foundation (Greece); Italian Association for
Research on Cancer (AIRC) and National Research Council (Italy); Dutch
Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer
Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON
(Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics
Netherlands (the Netherlands), NordForsk (Centre of Excellence programme
HELGA; 070015)(Norway); Health Research Fund (FIS), Regional Governments
of Andaluca, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC
(RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and
Regional Government of Skne and Vsterbotten (Sweden); Cancer Research
UK, and Medical Research Council (United Kingdom).
Bhoo-Pathy was supported by the European Union, AsiaLink program (grant
no MY/AsiaLink/044 (128713)), and the Ministry of Higher Education,
Malaysia (High Impact Research Grant (UM.C/HIR/MOHE/06)).
The respective local ethical committees, which approved this study are the
Local Ethical Committee for Copenhagen and Frederiksberg Municipalities
(Denmark); French National Commission for Data Protection and Privacy
(France); Ethics Committee of the Medical Association of the State of
Brandenburg, and Ethical Committee of the Medical Faculty, Heidelberg
University (Germany); Ethics Committee of the University of Athens Medical
School (Greece); Ethical Committee of the National Institute for Cancer (Italy);
Institutional Review Board of the University Medical Center Utrecht, and
Medical Ethical Committee of TNO Nutrition and Food Research (the
Netherlands); Regional Committee for Medical and Health Research Ethics
(REC-North)(Norway); Ethical Committee for Clinical Research (CEIC: Comit
de tica de Investigacin Clnica) Barcelona, and Ethics Committee of the
Bellvitge Hospital (Spain); Regional Ethical Review Board of Ume, and Ethical
Committee of the Faculty of Medicine, Lund University (Sweden); Norfolk
and Norwich Ethics Committee, and Scotland A Research Ethics Committee
(United Kingdom).
The International Agency for Research on Cancer provided administrative,
technical and material support in managing the EPIC database, and was
involved in the manuscript preparation, and decision to submit for
publication. All other funders did not play any role in this study.
Author details
1
Julius Center for Health Sciences and Primary Care, University Medical
Center, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. 2Department of
Social and Preventive Medicine, Faculty of Medicine, Julius Centre University
of Malaya, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia.
3
National Clinical Research Centre, Kuala Lumpur Hospital, Ministry of Health,
Kuala Lumpur, Malaysia. 4School of Public Health, Imperial College London,
London, UK. 5National Institute of Public Health and the Environment (RIVM),
Bilthoven, The Netherlands. 6Department of Gastroenterology and
Hepatology, University Medical Centre, Utrecht, The Netherlands.
7
Department of Public Health, Section for Epidemiology, Aarhus University,
Aarhus, Denmark. 8Danish Cancer Society, Institute of Cancer Epidemiology,
Copenhagen, Denmark. 9Inserm, Centre for Research in Epidemiology and
Population Health (CESP), U1018, Nutrition, Hormones, and Womens Health
Team, Institut Gustave Roussy, F-94805 Villejuif, France. 10Universit Paris Sud
11, UMRS 1018, F-94807 Villejuif, France. 11Department of Cancer
Epidemiology, German Cancer Research Center, Heidelberg, Germany.
12
Department of Epidemiology, German Institute of Human Nutrition,
Potsdam-Rehbruecke, Germany. 13Department of Hygiene, Epidemiology and
Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies,
University of Athens Medical School, 75 M. Asias Avenue, Goudi, GR-115 27
Athens, Greece. 14Hellenic Health Foundation, 10-12 Tetrapoleos Street,
GR-115 27 Athens, Greece. 15Nutritional Epidemiology Unit, Fondazione
IRCCS Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milan, Italy.
16
Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico
II, Via Pansini, 5 80131 Naples, Italy. 17Molecular and Nutritional Epidemiology
Unit, Cancer Research and Prevention Institute ISPO, Florence, Italy.
18
Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, ASP
7, Ragusa, Italy. 19HuGeF Foundation and CPO-Piemonte, Torino, Italy.
20
Division of Human Nutrition, Wageningen University, Wageningen, The
Netherlands. 21Department of Community Medicine, Faculty of Health
Sciences, University of Troms, The Arctic University of Norway, Troms,
Norway. 22Public Health and Participation Directorate, Health and Health
Care Services Council, Asturias, Spain. 23Unit of Nutrition, Environment and
Cancer, Cancer Epidemiology Research Programme, Catalan Institute of
Oncology (ICO-IDIBELL), Barcelona, Spain. 24Escuela Andaluza de Salud
Pblica, Instituto de Investigacin Biosanitaria de Granada (Granada.ibs),
Granada, Spain. 25Consortium for Biomedical Research in Epidemiology and
Public Health (CIBER Epidemiologa y Salud Pblica-CIBERESP), Madrid, Spain.
26
Department of Epidemiology, Murcia Health Council, Murcia, Spain.
27
Navarre Public Health Institute, Pamplona, Spain. 28Public Health Division of
Gipuzkoa, Instituto Investigacin Sanitaria, San Sebastian, Spain.
29
Department of Clinical Sciences in Malm/Nutrition Epidemiology, Lund
University, Malm, Sweden. 30Department of Odontology, Ume University,
Ume, Sweden. 31Department of Public Health and Clinical Medicine,
Nutritional Research, Ume University, Umea, Sweden. 32University of
Cambridge School of Clinical Medicine, Cambridge, UK. 33Medical Research
Council, Epidemiology Unit, Cambridge, UK. 34Cancer Epidemiology Unit,
University of Oxford, Richard Doll Building, Roosevelt Drive, Oxford OX3 7LF,
UK. 35International Agency for Research on Cancer, Lyon, France. 36Centre for
Primary Care and Public Health, Barts and The London School of Medicine,
Queen Mary University of London, London, UK.
Page 11 of 12
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Received: 25 May 2014 Accepted: 20 January 2015

24.
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Bhoo-Pathy et al.

Breast Cancer Research (2015) 17:15

Coffee and tea consumption and risk of pre- and

Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15

(Continued from previous page)

We determined the association between coffee (total,

This study pertains to female participants of the EPIC

Diet was assessed using country-specific questionnaires

Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15

Follow-up was based on linkage with population cancer

2009, and July 2005, respectively. Loss to follow-up was

Multivariable Cox regression was used to examine the

Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15

As data on hormone receptor status was only available

attained tertiary education, and were more likely to have

While moderately low intake of total coffee consumption

There seemed to be no association between caffeinated

Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15

Age at recruitment (mean (years))

Familial breast cancer (%)

Age at menarche (% <12 years)

Oral contraceptive use (% ever)

Age at first delivery (% < 20 years)h

Breastfed offsprings (% ever)

Menopausal hormone use (% ever)

Physically inactivei (%)

BMI (mean (kg/m2))

Alcohol intake (median (g/day))

Energy intake (mean (kcal/day))

Fat intake (mean (g/day))

Fruits intake (mean (g/day))

Vegetable intake (mean (g/day))

Tead intake (median (ml/day))

Coffeej intake (median (ml/day))

a linear trend for lower risk of breast cancer with increasing

As compared to decaffeinated coffee consumers with

Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15

Table 2 Total coffee consumption and risk of breast cancera

Per 100 mls

Number of breast cancers

Premenopausal breast cancers

Adjusted Hazard Ratio (95% CI)h

Adjusted Hazard Ratio (95% CI)i

Adjusted Hazard Ratio (95% CI)d

Adjusted Hazard Ratio (95% CI)e

Adjusted Hazard Ratio (95% CI)f

Adjusted Hazard Ratio (95% CI)g

cancer. Within consumers of decaffeinated coffee, no

Tea consumption was neither statistically significantly

Bhoo-Pathy et al. Breast Cancer Research (2015) 17:15

Table 3 Caffeinated coffee consumption and risk of breast cancera

No. of breast cancers

Premenopausal breast cancers

Adjusted Hazard Ratio (95% CI)d

Adjusted Hazard Ratio (95% CI)e

Adjusted Hazard Ratio (95% CI)f

Adjusted Hazard Ratio (95% CI)g

Daily caffeinated coffee intake

Per 100 mls

Analysis by cohort-wide intake