1. Night work and breast cancer: A population-based case–control
study in France (the CECILE study)
Florence Menegaux1,2
, There`se Truong1,2
, Antoinette Anger1,2
, Emilie Cordina-Duverger1,2
, Farida Lamkarkach1,2
,
Patrick Arveux3
, Pierre Kerbrat4
, Jo€elle Fevotte5
and Pascal Guenel1,2,5
1
Inserm, CESP Center for research in Epidemiology and Population Health, U1018, Environmental Epidemiology of Cancer, Villejuif, France
2
Univ Paris-Sud, UMRS 1018, Villejuif, France
3
Center Georges-Franc¸ois Leclerc, Departement d’informatique medicale, Dijon, France
4
Center Euge`ne Marquis, Rennes, France
5
Institut de Veille Sanitaire (InVS), Department of Occupational Health, Saint-Maurice, France
Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the
role of night work in a large population-based case-control study carried out in France between 2005 and 2008. Lifetime
occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and
1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR 5 1.27
[95% confidence interval 5 0.99–1.64]). Odds ratios were 1.35 [1.01–1.80] in women who worked on overnight shifts, 1.40
[1.01–1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01–2.03] in those who worked less than
three nights per week on average. The odds ratio was 1.95 [1.13–3.35] in women employed in night work for 4 years before
their first full-term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more
susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer,
particularly in women who started working at night before first full-term pregnancy.
Breast cancer is the most common cancer in women world-
wide with an annual incidence of $100 cases per 100,000 in
developed countries. It is estimated that over 1,300,000
women are diagnosed with breast cancer each year around
the world,1
and 53,000 in France.2
Recognized risk factors for breast cancer include genetic
mutations, family history of breast cancer, and several
aspects of reproductive history, but lifestyle, environmental,
or occupational causes of breast cancer are incompletely
identified.3
Following the publication of studies indicating a
possible role of night shift work in breast cancer, the Inter-
national Agency for Research on Cancer (IARC) in 2007
classified shift work that involves circadian disruption as
probably carcinogenic to humans, on the basis of sufficient
evidence in experimental animals and limited evidence of car-
cinogenicity in humans.4
Whether night work is implicated in
breast cancer etiology is of major importance for public health
because of the increasing number of women working on a non-
standard day schedule in modern societies. In 2005, for exam-
ple, 11% of European women were working on shifts that
included night work.5
Overall, among 12 epidemiological studies conducted so
far to investigate the association between night work and
breast cancer,6–17
eight reported positive associations,6–
10,14,15,17
of which six were cohort studies of nurses8–10,14,15
or radio and telegraph operators17
enrolled in shift work, and
two were population-based studies where night work was
assessed in a wide range of occupations.6,7
Other studies did
not report an association with breast cancer.11–13,16
Although
the body of evidence generally points to a role of night work
in breast cancer occurrence, there is a need of additional
studies to better identify the characteristics of night work
that may lead to an increased risk.18
Several mechanistic hypotheses for how shift work may
be related to cancer have been reviewed recently.19
They
include exposure to light at night that suppresses the noc-
turnal peak of melatonin and its associated anticarcinogenic
effects; disruption of the circadian rhythm regulated by sev-
eral ‘‘clock’’ genes controlling cell proliferation and apopto-
sis; repeated phase shifting leading to internal desynchroni-
zation and defects in the regulation of the circadian cell
cycle; and sleep deprivation that alters the immune
function.
Key words: case-control study, breast cancer, circadian disruption
Grant sponsor: Agence Nationale de securite sanitaire de
l’alimentation, de l’environnement et du travail (ANSES); Grant
number: 2010/2/2073; Grant sponsors: Agence Nationale de la
Recherche (ANR); Fondation de France; Institut National du Cancer
(INCA); Ligue contre le Cancer Grand Ouest; Association pour le
recherche contre le cancer (ARC)
DOI: 10.1002/ijc.27669
History: Received 27 Jan 2012; Accepted 24 May 2012; Online 12
June 2012
Correspondence to: Pascal Guenel, MD, PhD, CESP, for research
in Epidemiology and Population Health, U1018, Environmental
Epidemiology of Cancer, 16 av. Paul Vaillant Couturier, F-94807,
Villejuif, France, E-mail: pascal.guenel@inserm.fr
Epidemiology
Int. J. Cancer: 132, 924–931 (2013) VC 2012 UICC
International Journal of Cancer
IJC

2. The human breast undergoes several stages of maturation
throughout life, and may be particularly susceptible to carci-
nogens when exposure occurs during periods of mammary
gland development and differentiation such as puberty or
pregnancy.20
Although measuring environmental exposures
during critical periods of breast development in a woman’s
lifetime is a key issue for identifying exposures that may lead
to breast cancer later in life, the role of night work during
these critical exposure windows has not been specifically
investigated in epidemiological studies. Full differentiation of
the mammary gland occurs during first childbirth and lacta-
tion.21–23
It can thus be hypothesized that the risk of breast
cancer is particularly elevated when night work involving cir-
cadian disruption occurs in the period of life before first full-
term pregnancy, i.e., when mammary gland cells are incom-
pletely differentiated.
We conducted a large population-based case-control study
in France (CECILE) to investigate the role of environmental
and genetic factors in breast cancer that included data on
lifelong occupational history. In the present article, we ana-
lyzed the role of type, duration and frequency of night work
in breast cancer. We also focused on night work in the pe-
riod before first full-term pregnancy as a possible critical
window of exposure.
Material and Methods
Study population
Eligible cases were women aged 25–75 years, newly diagnosed
for breast cancer between 2005 and 2007 and residing in the
French departements of ‘‘Coˆte d’Or’’ or ‘‘Ille-et-Vilaine’’
(administrative areas) at the time of diagnosis. Patients were
recruited in the main cancer hospital of each area, as well as
from smaller public and private hospitals that also recruited
breast cancer patients, by specifically trained investigators. All
breast cancer diagnoses were confirmed histologically. Among
the 1,553 eligible cases identified during the study period,
163 refused to participate, 151 women could not be contacted
and 7 died before the interview. Finally, 1,232 (79%) incident
breast cancer cases were included in the study.
Controls were selected among general population women
free of cancer and resident in the study areas at the time of
the cases’ diagnoses. For including controls, quotas by age
were established as a preliminary to yield the control group
similar to the case group in terms of age to achieve fre-
quency-matching (10-year age group). Quotas by socio-eco-
nomic status (SES) were also set a priori to control for poten-
tial selection bias arising from differential participation rates
across SES categories. These quotas by SES were calculated
from the census data available in each study area, to obtain a
distribution by SES among controls identical to the SES dis-
tribution among general population women, conditionally to
age. The recruitment of controls was conducted as follows:
phone numbers of private homes were selected at random
from the telephone directory of each study area where
unlisted numbers had first been recreated. A phone number
was dialed up to 15 times at different times of the day and
different days of the week until contact could be established
with the residents. When a woman was living in the resi-
dence reached by phone, she was invited to participate to the
study, as long as the predefined quota corresponding to her
age group and socioeconomic status (SES) was not com-
pleted. When the quota was exceeded, the woman was
excluded. To obtain the desired number of controls within
the limits of age and SES categories, $30,000 phone numbers
were dialed for identifying 1,731 eligible controls. Among
these, 1,317 (76%) accepted to participate to an in-person
interview and were included in the study.
The study was approved by the French Ethic Committee
(Jan 2005), the National Data Protection Commission (Dec
2004) and the Advisory Committee on the Treatment of
Health Research Information (Apr 2004). All participants
signed informed consent before inclusion.
Data collection
A standardized questionnaire was administered during in-
person interviews by trained interviewers, to obtain informa-
tion on demographic and socioeconomic characteristics,
reproduction, medical history, family history of cancer, diet,
lifestyle factors, residential and occupational history over the
lifetime. A blood sample was also collected during interview.
For each job held for at least 6 consecutive months, we
obtained a description of the work tasks, work places, occu-
pational exposures and work schedules. Women were asked
whether they had worked for at least 1 hr between 11:00 pm
and 5:00 am during all or part of each job. We characterized
any night work period with the month and the year of begin-
ning and ending, the usual number of nights per week, and
the hour when the night shift started and ended. Any night
What’s new?
Data on lifelong occupational history collected as part of a population-based study conducted in France was used to
investigate the role of night work in breast cancer. The results indicate that night work increases breast cancer risk,
particularly in women who worked night shifts before their first full-term pregnancy. The findings suggest that incompletely
differentiated cells of the mammary gland before a woman’s first childbirth may be particularly susceptible to the potentially
carcinogenic effects of circadian disruption.
Epidemiology
Menegaux et al. 925
Int. J. Cancer: 132, 924–931 (2013) VC 2012 UICC

3. work period was categorized as overnight (night shift of 6
consecutive work hours or more spanning the time period
11:00 pm–5:00 am), late evening (night shift ending between
11:00 pm and 3:00 am), or early morning (night shift starting
between 3:00 and 5:00 am).
Statistical analysis
Unconditional logistic regression models were used to esti-
mate odds ratios (OR) and their 95% confidence intervals
(CI) using women who had never worked at night as the ref-
erence group. Analyses were systematically adjusted for the
original matching variables, i.e., age (5-year period) and study
area, and for well-established risk factors for breast cancer
categorized as follows: age at menarche (12, 12:reference,
13, 14, 15 years and more), age at first full-term pregnancy
(22, 22–24:reference, 25–27, 27 years), parity categorized
(nulliparous:reference, 1, 2, 3, 4þ children), current use of
menopausal hormone therapy (Yes, No), family history of
breast cancer in first-degree relatives (Yes, No), body mass
index according to the WHO categories (18.5, 18.5–24:ref-
erence, 25–30, 30), alcohol consumption ( 3 drinks/week:-
reference, 4–7 drinks/week, 8–14 drinks/week, 14 drinks/
week), and tobacco consumption (Never smokers: reference,
former smokers, current smokers). Duration of night work
was categorized into two groups according to the median
value among controls (4.5, !4.5 years or 4, 4 years for
the analysis of night work before first full-term pregnancy).
The average number of nights per week was categorized into
two groups according to the median of the distribution
among controls (3, !3). Analyses were also conducted after
stratification by age group (55 years, !55 years) used as a
proxy of menopausal status.
We also conducted analysis according to estrogen- or pro-
gesterone-receptor status (ER-positive or ER-negative, PR-
positive or PR-negative), and histological subtypes of breast
cancer using polytomous logistic regression models, but
results were not modified and are not shown.
Analyses were performed using SAS software (version 9.2,
Cary, NC).
Results
We included 1,232 breast cancer cases and 1,317 controls.
The distributions by age, study area and socioeconomic char-
acteristics are shown in Table 1. Cases and controls were
similarly distributed in terms of age and study area (stratifi-
cation variables). Cases were more frequently single and had
higher education levels than the controls.
Consistently with the literature, we found that the follow-
ing variables were associated with breast cancer (Table 2):
early age at menarche, late age at first full-term pregnancy,
low parity, current use of menopausal hormone therapy, low
body mass index in premenopausal women, lack of physical
activity and family history of breast cancer in first-degree rel-
atives. No association was apparent between breast cancer
and alcohol consumption, or high BMI in postmenopausal
women.
Night work
Overall, 311 women (12%) had ever worked during night shifts
(Table 3). Overnight work was the most frequent type of night
work schedule (n ¼ 222) followed by late evening work (n ¼
80) and early morning work (n ¼ 21). Night work was more
common among cases than among controls (OR ¼ 1.27 [CI ¼
0.99–1.64]) (Table 3). The odds ratio for overnight work (OR
¼ 1.35 [CI ¼ 1.01–1.80]) was slightly higher than the odds ra-
tio for late evening work (OR ¼ 1.25 [CI ¼ 0.79–1.98]). Early
morning shift was not associated with breast cancer.
Table 1. Tumor characteristics of breast cancer and
sociodemographic characteristics of cases and controls in the
CECILE study
Cases;
n ¼ 1,232
(%)
Controls;
n ¼ 1,317
(%) p
Histology
Ductal 980 (79.5)
Lobular 142 (11.5)
Mixed 25 (2.0)
Others 85 (7.0)
Hormone receptor status
ERþ/PRþ 794 (64.4)
ERÀ/PRÀ 171 (13.9)
ERþ/PRÀ 158 (12.8)
ERÀ/PRþ 10 (0.8)
Age at reference date (years)1
0.79
25–34 43 (3.5) 47 (3.6)
35–44 182 (14.9) 185 (14.1)
45–54 377 (30.5) 396 (30.0)
55–64 360 (29.2) 373 (28.4)
65–74 270 (21.9) 316 (23.9)
Study area1
0.12
Ile-et-Vilaine 841 (68.3) 861 (65.4)
Coˆte d’Or 391 (31.7) 456 (34.6)
Marital status2
0.03
Married or marital life 908 (73.7) 1,009 (76.6)
Single 86 (7.0) 58 (4.4)
Divorced or separated 135 (11.0) 129 (9.8)
Widow 103 (8.3) 121 (9.2)
Educational level2
0.02
Primary school 275 (23.3) 300 (22.8)
Basic secondary school 438 (35.6) 515 (39.1)
Secondary school 168 (13.6) 196 (14.9)
University education 351 (28.5) 305 (23.2)
1
Stratification variables. 2
p value adjusted for age and study area.
Epidemiology
926 Night work and breast cancer
Int. J. Cancer: 132, 924–931 (2013) VC 2012 UICC

4. Table 2. Odds ratios associated with family history of breast cancer, reproductive factors, lifestyle factors and body mass index in the CECILE
study
Cases; n ¼ 1,232 (%) Controls; n ¼ 1,317 (%) OR1
95% IC2
Family history of breast cancer in first-degree relatives
No 1,017 (82.6) 1,173 (89.1) 1.00 Reference
Yes 213 (17.3) 139 (10.6) 1.77 (1.40–2.23)
Age at menarche (years)
12 224 (18.4) 212 (16.3) 1.06 (0.83–1.36)
12 294 (24.2) 300 (23.0) 1.00 Reference
13 287 (23.6) 288 (22.1) 1.00 (0.79–1.26)
14 227 (18.7) 264 (20.2) 0.86 (0.68–1.10)
15þ 184 (15.1) 240 (18.4) 0.77 (0.60–0.99)
Age at first full-term pregnancy (years)
22 266 (24.4) 355 (28.9) 0.91 (0.73–1.14)
22–24 311 (28.4) 387 (31.4) 1.00 Reference
25–27 247 (22.4) 285 (23.2) 1.10 (0.88–1.39)
27 272 (24.8) 203 (16.6) 1.71 (1.34–2.17)
Parity
Nulliparous 136 (11.0) 87 (6.6) 1.00 Reference
1 195 (15.8) 175 (13.3) 0.72 (0.52–1.02)
2 484 (39.3) 469 (35.6) 0.64 (0.47–0.86)
3 294 (23.9) 398 (30.2) 0.45 (0.33–0.62)
4þ 123 (10.0) 188 (14.3) 0.40 (0.28–0.57)
Current use of menopausal hormone therapy
No 998 (81.0) 1,109 (84.2) 1.00 Reference
Yes 173 (14.0) 140 (10.6) 1.35 (1.05–1.73)
Physical activity
Never 388 (31.5) 365 (27.7) 1.00 Reference
At least 1 hr/week during 1 year 844 (68.5) 952 (72.3) 0.82 (0.69–0.98)
Alcohol
Never or 3 drink/week 960 (77.9) 993 (75.4) 1.00 Reference
4–7 drink/week 155 (12.6) 187 (14.2) 0.83 (0.66–1.05)
8–14 drink/week 67 (5.4) 87 (6.6) 0.76 (0.54–1.06)
14 drink/week 50 (4.1) 50 (3.8) 1.02 (0.68–1.04)
Body mass index (kg mÀ2
)
Women 50 years
18.5 28 (7.2) 15 (3.4) 1.85 (0.96–3.56)
18.5–24 276 (71.3) 285 (64.0) 1.00 Reference
25–30 57 (14.7) 95 (21.3) 0.61 (0.42–0.89)
30þ 26 (6.7) 50 (11.2) 0.54 (0.33–0.90)
Women ! 50 years
18.5 16 (1.9) 20 (2.3) 0.84 (0.43–1.65)
18.5–24 438 (52.1) 438 (50.3) 1.00 Reference
25–30 254 (30.2) 266 (30.6) 0.98 (0.78–1.22)
30þ 132 (15.7) 146 (16.8) 0.93 (0.71–1.22)
1
Adjusted for age and study area. 2
95% CI: 95% confidence interval.
Epidemiology
Menegaux et al. 927
Int. J. Cancer: 132, 924–931 (2013) VC 2012 UICC

5. Duration of night work of 4.5 or more years was associ-
ated with an OR of 1.40 [CI ¼ 1.01–1.92]. Working over-
night for 4.5 or more years yielded a similar odds ratio of
1.40 [CI ¼ 0.96–2.04].
The odds ratio in women who worked at night, less than
three nights per week on average was 1.43 [CI ¼ 1.01–2.03],
whereas it was only 1.14 [CI ¼ 0.82–1.59] in women who
worked at night !3 nights per week. Similarly, the ORs for
overnight shifts less than three nights per week and !3
nights per week were 1.61 [CI ¼ 1.07–2.42] and 1.13 [CI ¼
0.76–1.68], respectively.
In the analyses combining the duration of night work and
the average number of nights per week, the association with
breast cancer was particularly apparent among night workers
of long duration (!4.5 years) working less than three nights
per week on average (OR ¼ 1.83 [CI ¼ 1.15–2.93]). This
association was more pronounced when only overnight work
was considered (OR ¼ 2.09 [CI ¼ 1.26–3.45]).
In analyses restricted to parous women, we investigated
the effect of night work before or after first full-term preg-
nancy (FFTP) (Table 4). The odds ratio for breast cancer in
women who ever worked at night before FFTP was 1.47 [CI
¼ 1.02–2.12] as compared to never night workers, whereas it
was 1.09 [CI ¼ 0.77–1.55] in women who started working at
night after FFTP (Table 4). The odds ratio for night work
before FFTP was stronger among women who had been
working at night for 4 years before FFTP (OR ¼ 1.95 [CI
¼ 1.13–3.35]), and in those who worked at night less than
Table 3. Odds ratios for breast cancer associated with duration, frequency and type of night work among women of the CECILE study
Cases; n ¼ 1,232 (%) Controls; n ¼ 1,317 (%) OR1
95% CI2
Never worked at night 1,068 (86.7) 1,170 (88.8) 1.00 reference
Ever worked at night 164 (13.3) 147 (11.2) 1.27 (0.99–1.64)
Type of night work
Late evening3
42 (3.4) 38 (2.9) 1.25 (0.79–1.98)
Early morning4
9 (0.7) 12 (0.9) 0.90 (0.36–2.21)
Overnight5
120 (9.7) 102 (7.7) 1.35 (1.01–1.80)
Total duration of night work periods (years)
4.5 66 (5.4) 69 (5.2) 1.12 (0.78–1.60)
!4.5 98 (7.9) 78 (5.9) 1.40 (1.01–1.92)
Average frequency of night shifts (nights/week)
3 84 (6.8) 66 (5.0) 1.43 (1.01–2.03)
!3 80 (6.5) 81 (6.2) 1.14 (0.82–1.59)
Crossclassification of duration and frequency
4.5 years and 3 nights/week 30 (2.4) 35 (2.7) 1.04 (0.62–1.75)
4.5 years and !3 nights/week 36 (2.9) 34 (2.6) 1.19 (0.73–1.95)
!4.5 years and 3 nights/week 54 (4.4) 31 (2.4) 1.83 (1.15–2.93)
!4.5 years and !3 nights/week 44 (3.6) 47 (3.6) 1.10 (0.71–1.69)
Night work with overnight shifts
Total duration of night work periods with overnight shifts (years)
4.5 51 (4.3) 47 (3.7) 1.27 (0.83–1.94)
!4.5 69 (5.8) 55 (4.3) 1.40 (0.96–2.04)
Average frequency of overnight shifts (nights/week)
3 64 (5.4) 45 (3.5) 1.61 (1.07–2.42)
!3 56 (4.7) 57 (4.5) 1.13 (0.76–1.68)
Crossclassification of duration and frequency of overnight shifts
4.5 years and 3 nights/week 15 (1.3) 19 (1.5) 0.92 (0.45–1.89)
4.5 years and !3 nights/week 25 (2.1) 19 (1.5) 1.59 (0.86–2.96)
!4.5 years and 3 nights/week 49 (4.1) 26 (2.0) 2.09 (1.26–3.45)
!4.5 years and !3 nights/week 31 (2.6) 38 (3.0) 0.91 (0.55–1.50)
1
Adjusted for age, study area, parity, age at first full-term pregnancy, age at menarche, family history of breast cancer, current hormonal
replacement therapy, body mass index, tobacco and alcohol. 2
95% CI: 95% confidence interval. 3
Late evening: work shift ending between 11:00 pm
and 3:00 am. 4
Early morning: work shift starting between 3:00 am and 5:00 am. 5
Overnight: at least six consecutive work hours between 11:00 pm
and 5:00 am.
Epidemiology
928 Night work and breast cancer
Int. J. Cancer: 132, 924–931 (2013) VC 2012 UICC

6. three nights per week on average during this period of life (OR
¼ 2.24 [CI ¼ 1.35–3.71]). Combining duration and frequency
of night work before FFTP yielded an OR of 3.03 [CI ¼ 1.41–
6.50] for night work 4 years and 3 nights per week.
Analyses stratified by age group (55, !55 years) are pre-
sented in Table 5. Night work was more common among
younger (14.5%) than among older women (8.1%). Ever
working at night, or working at night before FFTP, was asso-
ciated with breast cancer in women below 55 years. Among
older women, there was some evidence of an increased risk
of breast cancer in women with long duration of night work
and working less than three nights per week.
Discussion
In this study, we have shown that breast cancer risk is associated
with characteristics of night work, and provided new evidence
that night work may play a role in the occurrence of the disease.
The association of night work with breast cancer was mainly
observed in women working during overnight shifts, those who
worked at night for 4.5 or more years and less than three nights
per week on average. The association was stronger in women
who worked at night before their first full-term pregnancy than
in women who started working at night later in life.
Overall, based on the available epidemiologic litera-
ture,8,9,12,13,24
the evidence of an association between night
work and breast cancer has been seen as limited. However,
cohort studies of nurses involved in night shift work8–10,14,15
have been more consistent than population-based studies.6,7
In these population-based studies, the large number of occu-
pational groups with various night work patterns, and the
lack of standardization of exposure assessment may explain
some of the inconsistencies, because the categories defining
type, duration and frequency of night work were based on
cut-off points that varied across studies, and may represent
different degrees of circadian disruption. It has been sug-
gested that several key domains should be used to better cap-
ture circadian disruption based on detailed information on
night work in epidemiological studies.18
Among those
domains were the rotating type of night-shift work, direction
and rate of rotation, and the number of consecutive nights at
work. It was also suggested to collect data on sleep habits,
and on subject chronotype.
In the present population-based study, our questionnaire
did not allow to go as deeply in the description of the night
shifts as recommended in this article, due to large differences
between night shift systems across occupations. Nevertheless,
we were able to categorize the type of night work using time
schedule data (late evening, overnight, early morning), and
examined the duration of night work in years as well as the
average number of nights per week.
We found that breast cancer risk increased for duration of
night work 4.5 years, a much shorter period than in cohort
Table 4. Odds ratios for breast cancer associated with night work after or before first full-term pregnancy (FFTP), and according to night work
characteristics before FFTP among parous women of the CECILE study
Cases; n ¼ 1,096 (%)1
Controls; n ¼ 1,230 (%)1
OR2
95% CI3
Never worked at night 954 (87.0) 1,093 (88.9) 1.00 reference
First night work after FFTP 66 (6.0) 78 (6.3) 1.09 (0.77–1.55)
Night work before FFTP 76 (6.9) 59 (4.8) 1.47 (1.02–2.12)
Type of night work before FFTP
Late evening4
18 (1.6) 11 (0.8) 1.89 (0.87–4.08)
Early morning5
6 (0.5) 9 (0.7) 1.09 (0.38–3.12)
Overnight6
52 (4.7) 39 (3.2) 1.49 (0.96–2.32)
Total duration of night work periods before FFTP (years)
4 years 33 (3.0) 36 (2.9) 1.15 (0.70–1.89)
4 years 43 (3.9) 23 (1.9) 1.95 (1.13–3.35)
Average frequency of night shifts before FFTP (nights/week)
3 nights/week 47 (4.3) 26 (2.1) 2.24 (1.35–3.71)
!3 nights/week 29 (2.6) 33 (2.7) 0.96 (0.56–1.62)
Crossclassification of duration and frequency of night shifts before FFTP
4 years and 3 nights/week 21 (1.9) 16 (1.3) 1.75 (0.89–3.42)
4 years and !3 nights/week 12 (1.1) 20 (1.6) 0.72 (0.34–1.51)
4 years and 3 nights/week 26 (2.4) 10 (0.8) 3.03 (1.41–6.50)
4 years and !3 nights/week 17 (1.5) 13 (1.1) 1.30 (0.61–2.77)
1
Analysis performed in women with children only. 2
Adjusted for age, study area, parity, age at first full term pregnancy, age at menarche, family
history of breast cancer, current hormonal replacement therapy, body mass index, tobacco and alcohol. 3
95% CI: 95% confidence interval. 4
Late
evening: work shift ending between 11:00 pm and 3:00 am. 5
Early morning: work shift starting between 3:00 am and 5:00 am. 6
Overnight: at least
6 consecutive work hours between 11:00 pm and 5:00 am.
Epidemiology
Menegaux et al. 929
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7. studies of nurses where the risk of breast cancer increased for
long durations (!20 years) of rotating night shift
work.8,10,14,15
Intriguingly, we also found that breast cancer incidence
was inversely related to the average number of working
nights per week. This finding requires clarification. It is not
consistent with a previous study reporting that the risk of
breast cancer increased with three or more working nights
per week in the 10 years before diagnosis.6
It has been postu-
lated however that the fewer nonday shifts in succession, the
less adaptation can occur.18
Our results of a smaller number
of nights per week associated with a higher risk of breast
cancer may thus reflect more frequent changes between night
and day schedules, conferring a higher degree of circadian
disruption. It is also possible that the number of nights per
week captured different types of rotating shift work patterns
that may be associated differently with breast cancer. The
number of consecutive nights has also been seen as a poten-
tially important characteristic of night work, as breast cancer
incidence was associated with rotating shifts of at least five
consecutive nights per month during at least 5 years among
nurses in one study.9
Unfortunately, we were not able to
assess the number of consecutive nights at work in our study.
We reported that breast cancer risk was higher in women
who started working at night before first full-term pregnancy,
particularly if the duration of night work before FFTP was
4 years, and if the number of nights per week was less than
3. Pesch et al. reported an odds ratio of breast cancer of 1.51
[CI ¼ 0.80–2.83] in women starting night shift work between
20 and 29 years of age, a period where most women give
birth for the first time.12
Our finding of a higher risk of
breast cancer related to night work exposure before FFTP is
of particular interest as it is compatible with the early life eti-
ological model for breast cancer, indicating that terminal dif-
ferentiation of the mammary gland cells occurs at first child-
birth and lactation.21–23,25,26
This finding supports the
hypothesis that incompletely differentiated mammary gland
cells may be more susceptible to the potentially carcinogenic
effects of circadian disruption during this period of life.19
Limits and strengths of the study
Our findings are based on a large carefully designed popula-
tion-based case-control study conducted to assess the role of
environmental, occupational and genetic factors in breast
cancer. The study power enabled to detect odds ratios of 1.5
or above assuming a prevalence of exposure among controls
of 10 percent, consistent with the proportion of night work-
ers among French27
and European women.5
Cases were women living in well-defined geographic areas
diagnosed with a breast cancer in 2005–2007. To minimize
selection bias, we aimed at recruiting all incident cases during
the study period in the study areas, by identifying breast can-
cer patients in the main cancer hospital of each area (Coˆte
d’Or and Ille-et-Vilaine), as well as from smaller public and
private hospitals that also recruited patients. To select the
controls from general population women in the same areas,
quotas by socioeconomic status (SES) were established to
yield the control group similar to the general population of
women of the same age in terms of SES. After the selection
process, we were able to compare the distribution by SES
between controls and the female general population in each
study area, and found no significant difference, indicating
that no major selection bias by SES had occurred. In addi-
tion, the proportion of night workers among controls was
Table 5. Odds ratios for breast cancer associated with night work characteristics by age group (55 or ! 55 years) among women of the
CECILE study
Women 55 years Women ! 55 years
Cases;
n ¼ 602 (%)
Controls;
n ¼ 627 (%) OR1
95% CI2
Cases;
n ¼ 630 (%)
Controls;
n ¼ 690 (%) OR1
95% CI2
Never worked at night 492 (81.7) 536 (85.5) 1.00 reference 576 (91.4) 634 (91.9) 1.00 reference
Ever worked at night 110 (18.3) 147 (14.5) 1.36 (0.98–1.87) 54 (8.6) 56 (8.1) 1.08 (0.72–1.63)
Type of night work
Overnightc
85 (14.1) 66 (10.5) 1.48 (1.03–2.13) 35 (5.6) 36 (5.2) 1.03 (0.62–1.71)
Total duration of night work (years)
4.5 49 (8.2) 41 (6.5) 1.40 (0.89–2.21) 17 (2.7) 28 (4.1) 0.63 (0.33–1.20)
!4.5 61 (10.1) 50 (8.0) 1.32 (0.87–2.00) 37 (5.9) 28 (4.1) 1.54 (0.91–2.61)
Average frequency of night shifts (nights per week)
3 61 (10.1) 51 (8.1) 1.32 (0.87–2.01) 23 (3.7) 15 (2.2) 1.82 (0.92–3.61)
!3 49 (8.2) 40 (6.4) 1.40 (0.89–2.21) 31 (4.9) 41 (5.9) 0.82 (0.50–1.36)
Night work before FFTPd
Ever worked at night Before FFTP 55 (10.5) 39 (6.7) 1.59 (1.05–2.40) 21 (3.7) 20 (3.1) 1.13 (0.62–2.06)
1
Adjusted for age, study area, parity, age at first full term pregnancy, age at menarche, family history of breast cancer, current hormonal
replacement therapy, body mass index, tobacco and alcohol. 2
95% CI: 95% confidence interval. 3
Overnight: at least 6 consecutive work hours
between 11:00 pm and 5:00 am. 4
Analysis conducted in parous women only.
Epidemiology
930 Night work and breast cancer
Int. J. Cancer: 132, 924–931 (2013) VC 2012 UICC

8. similar to that expected among women in France.27
Women
reporting night work in our study were employed in indus-
tries where night work is common, i.e., health and social
work, hotels and restaurants, transportation and communica-
tion, manufacture of chemicals, rubber and plastic products,
manufacture of motor vehicles, manufacture of food products
and beverages.18,27
The population-based design of the study
also provides some reassurance that the association between
breast cancer and night work is not restricted to a few occu-
pations with frequent night shifts such as nurses.
Although recall bias cannot be totally excluded, it was
minimized by the use of standardized questionnaires and the
similar interviewing conditions for cases and controls. More-
over, the study was conducted in 2005–2008, a period where
the carcinogenic potentials of night work was not a major
public concern in France. In addition, the mean number of
jobs and the total duration of employment reported by cases
and controls were similar.28
To address the possibility of confounding by well-estab-
lished risk factors for breast cancer, all models examining the
association between breast cancer and night work were
closely adjusted for potential confounders. Night work was
weakly associated with tobacco smoking, body mass index or
alcohol consumption, but adjusting for these variables in the
models did not change the results.
In conclusion, our results support a possible role of night
work in breast cancer, particularly if night work occurs
before first full-term pregnancy, and may reflect the link
between circadian disruption and mammary carcinogenesis.
To go further in the understanding of night work and circa-
dian disruption in cancer etiology, epidemiological studies
should better standardize night work definition across stud-
ies. Besides collecting data on work schedules over lifetime
work history, future epidemiological studies should assess the
subjects’ chronotype to better characterize circadian disrup-
tion. Investigations on genetic polymorphisms and/or epige-
netic changes in genes involved in circadian rhythm are also
of interest. Given the increasing prevalence of night work
among women in modern societies, scrutinizing the relation-
ship between night work and breast cancer constitutes a
major issue for public health and may have an impact on
work policy.
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