Original Article

Increased Risk of Severe Depression in Male

Partners of Women With Breast Cancer
Naoki Nakaya, PhD1,2,3; Kumi Saito-Nakaya, PhD1,2; Pernille Envold Bidstrup, PhD1; Susanne Oksbjerg Dalton, MD, PhD1;
Kirsten Frederiksen, PhD4; Marianne Steding-Jessen, PhD4; Yosuke Uchitomi, MD, PhD2;
and Christoffer Johansen, MD, PhD, DMSc1,5

BACKGROUND: A few small studies published to date have suggested that major psychosocial problems develop in
the partners of cancer patients; however, to the authors’ knowledge, no studies to date have addressed their risk for
severe depression. In a retrospective cohort study, the risk for hospitalization with an affective disorder of the male
partners of women with breast cancer was investigated, using unbiased, nationwide, population-based information.
METHODS: Followed were 1,162,596 men born between 1925 and 1973 who were aged
30 years at study entry,
resided in Denmark between 1994 and 2006, had no history of hospitalization for an affective disorder, and had lived
continuously with the same partner for at least 5 years. A Cox regression analysis included detailed clinical informa-
tion regarding the diagnosis and treatment of breast cancer and on annually updated socioeconomic and health-
related indicators obtained from national administrative and disease registers. RESULTS: During the 13 years of
follow-up, breast cancer was diagnosed in the partners of 20,538 men. On multivariable analysis, men whose partner
was diagnosed with breast cancer were found to be at an increased risk of being hospitalized with an affective
disorder (hazards ratio, 1.39; 95%confidence interval, 1.20-1.61), with a dose-response pattern for the severity of breast
cancer. Furthermore, men whose partner died after breast cancer had a significant, 3.6-fold increase in risk for an
affective disorder when compared with men whose partner survived breast cancer. CONCLUSIONS: The results of
the current study supported the hypothesis that men whose partner had breast cancer were at an increased risk for
hospitalization with an affective disorder. Cancer 2010;116:5527–34. V C 2010 American Cancer Society.

KEYWORDS: affective disorder, breast cancer, cohort study, Denmark, depression, partners.

During the past few decades, our understanding of the consequences of cancer has changed, with recognition not only
of physical but also of psychological and social effects.1,2 In response, various supportive psychosocial intervention strat-
egies have been designed, tailored to the problems that cancer patients face during the course of their disease.3-6 The extent
to which cancer affects not only patients but also their closest relatives was first addressed in a seminal article published
more than 20 years ago, in which House et al illustrated how several diseases can influence people close to the patient.7
The mechanism of this effect may involve several interacting pathways: the event may cause stress in the partner; it might
deprive the partner of emotional, social, and economic support; and it can influence the daily life and behavior of the
partner.7,8
The effect of cancer on the psychological well-being of the partner could result in increased risks of several psychiatric
disorders related to stressful life events, including neurotic, stress-related, somatoform, substance abuse-related, and affec-
tive disorders.
A recent population-based retrospective cohort study including 11,000 spouses of cancer patients indicated that risk
of psychiatric diseases was increased among spouses of cancer patients.9 In keeping with these findings, some of the previ-
ous studies on depression after a diagnosis of cancer in a spouse support an association,10-13 whereas others have reported
negative or null findings.14-16 The majority of the studies had several limitations, including small sample sizes of spouses

Corresponding author: Naoki Nakaya, PhD, Department of Psychosocial Cancer Research, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden
49, DK-2100 Copenhagen, Denmark; Fax: (011) 45 35 25 77 31; nakaya-thk@umin.ac.jp
1
Department of Psychosocial Cancer Research, Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; 2Psycho-Oncology Division,
Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan; 3Department of Nutrition and Dietetics, Faculty of Family and
Consumer Sciences, Kamakura Women’s University, Kamakura, Japan; 4Department of Statistics and Epidemiology, Institute of Cancer Epidemiology, Danish Can-
cer Society, Copenhagen, Denmark; 5National Centre for Cancer Rehabilitation Research, Institute of Public Health, Southern Danish University, Odense, Denmark
We thank Visti B. Larsen and Aslak H. Poulsen of the Institute of Cancer Epidemiology, Danish Cancer Society, for their assistance with the statistical analyses.
DOI: 10.1002/cncr.25534, Received: February 19, 2010; Revised: June 3, 2010; Accepted: June 14, 2010, Published online September 27, 2010 in Wiley Online
Library (wileyonlinelibrary.com)

Cancer December 1, 2010 5527

Original Article
with cancer (<200 subjects),10-16 and only a few small
studies did include a relevant comparison group.12,13 To the
best of our knowledge, none of the previous studies regarding
the risk of depression in partners of cancer patients used an
objectively defined state of depression, diagnosed years before
the study was conducted, and obtained from an administra-
tive, population-based and nationwide database to reduce the
risk for misclassification of the outcome under study as well
as recall and information bias.10-16
In a retrospective study with a cohort design, based
on a nationwide sample and register-based information,
we carefully examined the risk for hospitalization for an
affective disorder among the male partners of women in
whom breast cancer had been diagnosed. We focused
purely on the affective spectrum because these disorders
are severe, are commonly associated with stressful life
events, and more systematically lead to a psychiatric
diagnosis or hospitalization compared with other possibly
stress-related disorders.
MATERIALS AND METHODS
Study Population
Since 1968, all Danish residents have been registered in
the Central Population Register and assigned a unique
personal identification number that contains their date of
birth and sex. Individual information is kept under this
identification number in all national registries, ensuring
accurate linkage of information among these registries.17
We identified all 3.47 million persons who were born
between 1925 and 1973, who resided in Denmark in the
period between 1994 and 2006, and who entered the
cohort at aged
30 years without a previous cancer. Of
the total of 1,628,651 men identified, 1,170,582
had been either married or cohabiting with a partner
continuously for at least 5 years at the time of study
entry. Cohabitation was included because in Denmark,
>20%of all couples living together in 2002 were
unmarried.18 We defined cohabitation in our context as
2 persons of the opposite sex, aged >16 years, with a
maximum age difference of 15 years, living at the same
address in the absence of marriage, with no other adult in
residence. Information regarding cohabitation status as
well as death and emigration was obtained through
linkage to the Central Population Register.
Breast Cancers
We identified women in whom breast cancer had been
diagnosed through linkage with the Danish Breast Cancer
5528
Cooperative Group (DBCG). Since its establishment in
1977, nearly all new breast cancer patients have been
registered in the DBCG database.19 The DBCG has pre-
pared national guidelines for diagnostic and therapeutic
procedures in patients with primary invasive breast cancer,
which were later supplemented by guidelines for in situ
carcinomas and hereditary breast cancer.19 The infor-
mation on the breast cancers includes date of primary
surgery, tumor size (in mm), number of tumor-positive
lymph nodes, estrogen and progesterone receptor status,
chemotherapy and/or hormone therapy, radiotherapy,
and date of disease recurrence and/or death.
Affective Disorders
Information on hospitalization with affective disorders
was obtained from the nationwide Danish Psychiatric
Central Register,20 which contains information regarding
all admissions to Danish psychiatric inpatient facilities,
both psychiatric hospitals and psychiatric departments in
general hospitals, and, since 1995, information from
outpatient contacts. The admission record includes the
hospital department, the date of admission, the date of
discharge, 1 primary psychiatric diagnosis, and up to 3
auxiliary diagnoses. The affective disorders were classified
according to the eighth edition of the International Classi-
fication of Diseases (ICD-8)21 between 1969 and 1993
and according to ICD-1022 since 1994 by the following
codes: ICD-8 codes 296.09 to 296.99, 298.09 to 298.19,
300.19, and 300.49; and ICD-10 codes F30 to F39.
Socioeconomic and Demographic Indicators
Information regarding the socioeconomic characteristics
was obtained from the population-based Integrated Data-
base for Labour Market Research in Statistics Denmark,
which contains yearly data since 1980. The core variables
in the database are derived by linkage with the Central
Population Register, the taxation authorities, the Register
for Education Statistics, the Register Relating to
Unemployment, and a register of all companies with >1
employee. For all persons in the study population, we
obtained information at the individual level regarding
several demographic and socioeconomic variables for each
year of the study period.23,24 Four indicators were
defined: number of children living at home ages birth to
17 years (0, 1, or
2), highest attained educational level
(basic or high school, vocational education, higher educa-
tion, or unknown), disposable household income (lowest
[1st quartile], middle [2nd-3rd quartile], or highest [4th
quartile]), and affiliation to the work market (working,
Cancer December 1, 2010

unemployed or other, early retirement, or unknown). We
obtained information concerning the income of all family
members to estimate total family income.
Comorbidity
Using the Danish National Patient Register25 and the
Psychiatric Case Register,20 we obtained full histories of
any disease leading to hospitalization from 1978 and,
beginning in 1995, also outpatient visits by each study
participant through 2006. The information in these regis-
ters includes the dates of admission and discharge and
diagnoses coded according to the Danish modified ver-
sions of the ICD-821 and, from 1994 onward, ICD-10.22
On the basis of information from these registers, we
defined 3 health-related indicators to account for the
presence of chronic somatic and psychiatric comorbidity:
the Charlson index,17,26 alcohol-related mental disorders
(ICD-8 codes 291.09-39, 291.99, 303.09-29, 303.99,
and 393.09; and ICD-10 code F10), and schizophrenia
and other psychoses (ICD-8 code 295 and ICD-10 codes
F20 and F25).
Analyzed Cohort
Of the 1,170,582 men who had been living with a partner
for
5 years, we excluded 7951 men who had had an
affective disorder (n ¼ 7216), schizophrenia, or another
psychosis (n ¼ 735) before the beginning of follow-up
and 35 men who were censored (because of death, emigra-
tion, or remarriage) before the beginning of follow-up,
leaving 1,162,596 men (99.0%) for the analyses.
Statistical Analyses
We used Cox regression analysis to assess the risk for
hospitalization with an affective disorder after the diagno-
sis of breast cancer in a partner. The hazard ratio (HR) for
hospitalization with an affective disorder after having
experienced breast cancer in a partner compared with not
having experienced breast cancer in a partner was esti-
mated using the PHREG procedure in the SAS statistical
software package (version 9.1; SAS Institute, Cary, NC).
Follow-up time was counted from January 1 of the year in
which the man had lived continuously with the same
partner for 5 years, January 1 from the year the man
turned 30 years old, or January 1, 1994, whichever came
last and until the date of hospitalization with an affective
disorder; death; death of partner; emigration; onset of
schizophrenia; December 31, 2006; or new cohabiting
partner, whichever came first. The exposure variable (ie,
the diagnosis of breast cancer in the partner) was included
Cancer December 1, 2010
Depression in Partners of Cancer Patients/Nakaya et al
as a time-dependent variable. Thus, person-time before
the partner’s breast cancer diagnosis was counted as
unexposed, whereas person-time after the breast cancer
diagnosis was counted as exposed.
The HRs were adjusted for number of children,
highest attained educational level, disposable household
income, affiliation to the work market, Charlson index,
and history of alcohol-related mental disorders. Infor-
mation regarding these factors (except for age) was
extracted 2 years before the man’s date of entry to avoid
misclassification due to, for example, a change in socio-
economic or health status that might be related to the
presence of an as-yet undiagnosed breast cancer. To exam-
ine the effect and potential effect modification of the
factors included as confounders, we conducted separate
analyses of affective disorders according to the adjustment
factors. We determined whether the association between
the partner’s breast cancer and the risk of hospitalization
with an affective disorder was affected by interactions
with these variables. To assess whether the results were
influenced by change in cohabiting partner, we also con-
ducted analyses with no censoring at the date of new
cohabiting partner. In a sensitivity analysis of HRs of hos-
pitalization for an affective disorder according to time
since entry, we examined HRs in 3 intervals of follow-up
after the partner’s breast cancer diagnosis: 1 year, 2 to 3
years, and 4 to 13 years of follow-up. To assess whether
the risk for hospitalization with an affective disorder was
affected by the severity of the breast cancer, we also
estimated HRs for hospitalization with an affective
disorder according to breast cancer tumor size, number of
tumor-positive lymph nodes, estrogen and progesterone
receptor status, chemotherapy and/or hormone therapy,
and radiotherapy. In analyses of tumor size and number
of tumor-positive lymph nodes, P values for the linear
trends were calculated as a continuous variable in the
regression model (tumor size in mm and number of tu-
mor-positive lymph nodes). Among the men experiencing
a diagnosis of breast cancer in their partner, we assessed
the HRs for hospitalization with an affective disorder
according to the partner’s disease recurrence or death after
the breast cancer diagnosis, respectively. In these analyses,
follow-up time was counted from the date of the partner’s
breast cancer diagnosis until date of death, emigration,
new cohabiting partner, onset of schizophrenia, hospitali-
zation with an affective disorder, or December 31, 2006,
whichever came first. When examining breast cancer
recurrence as the exposure variable, person-time before
disease recurrence was counted as unexposed, person-time
5529
Original Article

Table 1. Socioeconomic, Demographic, and Health-Related Table 2. Clinical Characteristics at Entry into the Study of
Indicators for 1,162,596 Men at Entry: Denmark, 1994 20,538 Cases of Female Breast Cancer: Denmark 1994
Through 2006 Through 2006

Characteristic Subjects Clinical Characteristic No. (%)

Mean/median age (SD) y 45/44 (11) Tumor size, mm
a
0-10 3490 (17)
No. of children (%) 11-20 8894 (43)
0 551,623 (47) 21-50 7416 (36)
1 295,520 (25) ‡51 738 (4)
‡2 315,453 (27)
No. of tumor-positive lymph nodes
Highest attained educational level, no. (%)a 0 11,068 (54)
Basic or high school 369,364 (32) 6122 (30)
1-3
Vocational education 509,566 (44) ‡4 3348 (16)
Higher education 260,257 (22)
Unknown 23,409 (2) ER and PR statusa
Negative 4188 (20)
Disposable income, no. (%)a Positive 15,103 (74)
Lowest (1st quartile) 232,545 (20) 1247 (6)
Unknown
Middle (2nd-3rd quartile) 605,369 (52)
Highest (4th quartile) 324,682 (28) Chemotherapy and/or hormone therapy
None 6721 (33)
Affiliation to work market, no. (%)a Received 13,696 (67)
Working 996,134 (86) Unknown 121 (1)
Unemployed or other 104,665 (9)
Early retirement 29,150 (3) Radiotherapy
Unknown 32,647 (3) None 9413 (46)
a
Received 11,125 (54)
Charlson index, no. (%)
None 1,077,533 (93) ER indicates estrogen receptor; PR, progesterone receptor.
a
1 62,343 (5) Negative indicates that individual was negative for both ER and PR or
‡2 22,720 (2) negative for 1 and unknown for the other. Positive indicates ER-positive or
PR-positive disease.
Alcohol-related mental disorders, no. (%)a,b
Never 1,161,605 (99.9)
Ever 991 (0.1)

SD indicates standard deviation.
a
Information extracted 2 years before individual date of entry.
b
International Classification of Diseases (ICD)-8th revision codes 291.09,
291.19, 291.29, 291.39, 291.99, 303.09, 303.19, 303.29, 303.99, or 393.09;
and ICD-10 code F10.
after disease recurrence was counted as exposed, and cen-
suring took place at death of the partner. When examing
death after breast cancer in the partner as the exposure
variable: person-time before date of death of the partner
was counted as unexposed and person-time after date of
death was counted as exposed.
In all analyses, time since entry into the study was
used as the time scale and the baseline HR was stratified
by age at entry (30-34, 35-39, 40-44, 45-49, 50-54, 55-
59, 60-64, 65-69, and
70 years). All P values are 2-
sided, with a 2-sided a error level of 5%.
RESULTS
Of the 1,162,596 men, a total of 11,855,300 person-years
of follow-up were accrued, yielding a median follow-up of
13 years (range, 0-13 years). We identified 20,538 male
partners of women diagnosed with breast cancer. Of the
male partners, a total of 12,365 were hospitalized for an
affective disorder and among these men, a total of 180
had a partner who was diagnosed with breast cancer.
The socioeconomic, demographic, and health-
related indicators are listed in Table 1. A high percentage
of the men had no children, attained vocational educa-
tion, were working, and had no comorbidity.
The clinical characteristics of the breast cancers are
listed in Table 2. A high percentage of women with breast
cancer had tumors that measured 11 to 20 mm, had no
tumor-positive lymph nodes, and received chemotherapy
and/or hormone therapy as well as radiotherapy.
On multivariable Cox proportional regression anal-
ysis, men whose partner was diagnosed with breast cancer
were found to be at an increased risk of being hospitalized
with an affective disorder compared with men whose part-
ner was not diagnosed with breast cancer (HR, 1.39; 95%
confidence interval [95% CI], 1.20-1.61) (Table 3). In
analyses without censoring at the date of new cohabiting
partner, only small differences in results were observed
(HR, 1.39; 95% CI, 1.20-1.61).

5530 Cancer December 1, 2010

 Depression in Partners of Cancer Patients/Nakaya et al

Table 3. Multivariate HRs and 95% CIs for Hospitalization When we examined the risk of hospitalization for an
With an Affective Disorder by Exposure to Partner’s Breast
Cancer: Denmark, 1994 Through 2006a affective disorder according to different levels of clinical
variables among the women with breast cancer, we identi-
Variable Unexposed Exposed fied a consistently increased risk of affective disorders
Person-y of follow-up 11,724,718 130,582 concurrently with an increase in the disease severity,
No. of affective disorders 12,185 180
especially for tumor size (P for linear trend ¼ .003) and
Multivariate HR (95% CI) 1.00 (reference) 1.39 (1.20-1.61)
P — <.001 number of tumor-positive lymph nodes (P for linear
trend ¼ .002) (Table 4). Furthermore, we identified a
HR indicates hazard ratio; 95% CI, 95% confidence interval.
a
Multivariate HRs were adjusted for the number of children (0, 1, or
2), consistently increased risk for hospitalization with affec-
highest attained educational level (basic or high school, vocational, higher, tive disorders that did not appear to be influenced by
or unknown), disposable household income (lowest [1st quartile], middle
[2nd-3rd quartiles], or highest [4th quartile]), affiliation to the work market
receiving chemotherapy and/or hormone therapy and
(working, unemployed or other, early retirement, or unknown), Charlson radiotherapy. In the subgroup of men whose partner was
index (0, 1, or
2), and history of alcohol-related mental disorders (ever or
never). Time since entry into the study was used as the time scale. In all
diagnosed with breast cancer, the death of the breast can-
analyses, the baseline HR was stratified by age at entry (30-34, 35-39, 40- cer partner was associated with a 3.6-fold significant
44, 45-49, 50-54, 55-59, 60-64, 65-69, and
70 years). increased risk of hospitalization for an affective disorder.

Table 4. Multivariate HRs and 95% CIs for Hospitalization With an Affective Disorders According to Partner’s Clinical
Characteristics: Denmark, 1994 Through 2006

Clinical Statusa Unexposed Exposed

Tumor Size, mm 0-10 11-20 21-50
51
Person-y of follow-up 11,724,718 22,129 56,818 46,712 4923
No. of affective disorders 12,185 27 79 66 8
Multivariate HR(95% CI) 1.00 (reference) 1.26 (0.86-1.84) 1.41 (1.13-1.76) 1.40 (1.10-1.79) 1.64 (0.82-3.27)
P — .23 .003 .006 .16
P for linear trendb .003
No. of Tumor-Positive Lymph Nodes 0 1-3
4
Person-y of follow-up 11,724,718 72,723 37,633 20,226
No. of affective disorders 12,185 95 48 37
Multivariate HR(95% CI) 1.00 (reference) 1.30 (1.06-1.60) 1.32 (0.99-1.75) 1.85 (1.34-2.55)
P — .004 .06 <.001
P for linear trendb .002
ER and PR Statusc Positive Negative Unknownd
Person-y of follow-up 11,724,718 27,357 91,233 11,992
No. of affective disorders 12,185 45 116 19
Multivariate HR(95% CI) 1.00 (reference) 1.67 (1.24-2.23) 1.29 (1.07-1.54) 1.56 (0.99-2.44)
P — .001 .007 .05
Chemotherapy and/or Hormone Therapy None Received Unknownd
Person-y of follow-up 11,724,718 51,412 78,614 556
No. of affective disorders 12,185 70 109 1
Multivariate HR(95% CI) 1.00 (reference) 1.33 (1.05-1.68) 1.43 (1.18-1.73) 2.07 (0.29-14.66)
P — .02 <.001 .47
Radiotherapy None Received
Person-y of follow-up 11,724,718 68,282 62,300
No. of affective disorders 12,185 96 84
Multivariate HR(95% CI) 1.00 (reference) 1.37 (1.12-1.68) 1.41 (1.14-1.75)
P — .002 .002

HR indicates hazard ratio; 95% CI, 95% confidence interval; ER, estrogen receptor; PR, progesterone receptor.
a
Multivariate HRs were adjusted for the number of children (0, 1, or
2), highest attained educational level (basic or high school, vocational, higher, or
unknown), disposable household income (lowest [1st quartile], middle [2nd-3rd quartiles], or highest [4th quartile]), affiliation to the work market (working,
unemployed or other, early retirement, or unknown), Charlson index (0, 1, or
2), and history of alcohol-related mental disorders (ever or never). Time since
entry into the study was used as the time scale. In all analyses, the baseline HR was stratified by age at entry (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-
64, 65-69, and
70 years). Clinical characteristics were obtained at the time of diagnosis.
b
The analyses of linear trends were calculated as a continuous term in the regression model (tumor size in mm and tumor-positive lymph nodes in numbers).
c
Negative indicates that individual was negative for both ER and PR or negative for 1 and had unknown status for the other. Positive indicates ER-positive or
PR-positive disease.
d
Persons with unknown category were not included in the analysis of linear trend.

Cancer December 1, 2010 5531

Original Article

Table 5. Multivariate HRs and 95% CIs for Hospitalization With an Affective Disorder by Disease
Recurrence in or Death of Partner With Breast Cancer: Denmark, 1994 Through 2006a

Recurrence Death
No recurrence Recurrence No death Death
Person-y of follow-up 109,870 21,191 115,780 14,792
No. of affective disorders 139 41 122 58
Multivariate HR (95% CI) 1.00 (reference) 1.54 (1.09-2.19) 1.00 (reference) 3.63 (2.64-5.01)
P - .02 <.001

HR indicates hazard ratio; 95% CI, 95% confidence interval.

a
Multivariate HRs were adjusted for the number of children (0, 1, or
2), highest attained educational level (basic or high
school, vocational, higher, or unknown), disposable household income (lowest [1st quartile], middle [2nd-3rd quartiles], or
highest [4th quartile]), affiliation to the work market (working, unemployed or other, early retirement, or unknown), Charl-
son index (0, 1, or
2), and history of alcohol-related mental disorders (ever or never). Time since entry into the study
was used as the time scale. In all analyses, the baseline HR was stratified by age at entry (30-34, 35-39, 40-44, 45-49,
50-54, 55-59, 60-64, 65-69, and
70 years).

Experiencing disease recurrence in the partner was also
found to be significantly associated with an increased risk
of an affective disorder (Table 5).
In the sensitivity analysis of hospitalization for an
affective disorder according to time since entry, the HR was
1.36 (95 %CI, 0.85-2.17; N ¼ 23) for the first year of
follow-up, 1.40 (95% CI, 1.03-1.90; N ¼ 48) for 2 to
3 years of follow-up, and 1.66 (95% CI, 1.38-1.99, N ¼
109) for 4 to 13 years of follow-up. The risk for hospitaliza-
tion with an affective disorder was not found to be signifi-
cantly affected by adjustment for covariates (data not shown).
DISCUSSION
In this cohort study based on a large, nationwide, popula-
tion-based sample, with extensive control for confound-
ers, we found that the male partners of women in whom
breast cancer has been diagnosed were at a significantly
increased risk for severe depression. The observed associa-
tion might be explained by stress and a lack of social
support.27 Breast cancer in the partner might also lead to
changes in the lifestyle of the male partner, which could
affect the risk for affective disorders.28 It has been very
well established that family caregivers in general and those
in oncology in particular have a high risk of depression
because they experience chronic stress that affects their
physical state.29,30
In keeping with the results of the current study, 2
case-control studies of the risk for depression in the part-
ners of cancer patients that had small samples but relevant
comparison groups also found a significantly increased
risk in the exposed group.12,13 Although the outcomes of
these 2 studies are less marked than in the current study,
the results support the hypothesis that a partner’s cancer
diagnosis has an effect on the spouse’s risk for depression.
We identified a consistently increasing risk of affective
disorders based on breast cancer severity (tumor size, num-
ber of tumor-positive lymph nodes, and disease recurrence
or death after the breast cancer diagnosis). The severity of
the breast cancer influences the risk of the physical and
psychosocial effects of treatment in the woman, such as
lymphedema,31 cardiovascular disease,32 fatigue,33 depres-
sion,33 and anxiety.33 If the partner with breast cancer
experiences late effects, develops disease recurrence, or dies,
these events each may increase the psychological burden on
the man. In keeping with the results of the current study, a
community-based cohort study of 1046 elderly individuals
(aged
65 years), of whom 139 had experienced widow-
hood, indicated that widowhood was associated with an
increased risk of depression.34 Two follow-up studies also
demonstrated a significantly increased risk of depression
among individuals whose partner had cancer in the termi-
nal stage.10,15 Thus, the effect of breast cancer in a partner
on the man’s risk for hospitalization with depression might
depend both on the burden of late effects of the breast
cancer and treatment and the overall prognosis.15
Previously, we conducted a nationwide, population-
based study to determine whether cancer is followed by an
increased risk of divorce or separation in cohabiting part-
ners, which might explain the increased risk of severe
depression. We found an increased risk of divorce only
among women with cervical cancer.35
We studied the risk of affective disorders severe
enough to warrant hospitalization. Because such events
are rare, cases in both the exposed (137.8 per 100,000
person-years) and the unexposed (103.9 per 100,000
person-years) groups were small. Nevertheless, the diag-
nosis of an affective disorder by a psychiatrist followed by
hospitalization ensures that the risk of misclassification of

5532 Cancer December 1, 2010


the outcome under study is minimal. We speculate that
the effect would have been even stronger if we had used
outcomes such as antidepressant usage, referral to a
psychologist, or reduced quality of life.
The current study has several advantages, including
the design, which minimized selection bias. The data were
obtained from public administrative registers established
years before the study was initiated, thereby leaving little
room for information bias. The register-based data regard-
ing hospitalization for affective disorders and the clinical
data concerning breast cancer provided precise information
on the timing of both exposure and outcome. Cases of
breast cancer are recorded by the DBCG only if a detailed
pathology report is available, thus minimizing the risk of
misclassification of the exposure. Access to nearly complete
clinical data on the breast cancer cases made it possible to
examine the dose-response relation by disease severity, and
the findings further supported the results. In addition, we
were able to adjust for important confounding factors and
to include both officially married and cohabitating couples,
which is relevant in Western countries such as Denmark, in
which a substantial proportion of couples are not married.18
Men in this study were followed for a maximum of 13
years, and the results demonstrated that men whose partner
had been diagnosed with breast cancer were at a similarly
increased risk of hospitalization for an affective disorder
throughout the follow-up period.
The current study also had some limitations. The
men in this study were cancer free at baseline. Cancer
patients’ partners may be more likely to have cancer.36
Thus, exposed men in this study could potentially have
been more likely to be diagnosed with cancer and affective
disorders after a cancer diagnosis in a partner than unex-
posed men.37 The current study may have underestimated
the risk of affective disorders. We had no information
regarding lifestyle factors such as alcohol consumption,
physical activity, or dietary habits that might be associated
with the risk of depression as well as possibly breast cancer
in the partner due to shared lifestyle.38,39 The fact that
these potential confounding factors were not taken into
account might have resulted in an overestimation of the
true effect. This study focused only on the partners of
breast cancer patients, because we had access to detailed
clinical information for this group of patients on a
nationwide and population-based basis. We conducted a
further analysis focusing on the partners of patients with
cancer at any sites using the Danish Cancer Registry
dataset with follow-up until December 31, 2003. We
followed 1,116,829 men born between 1925 and 1973
Cancer December 1, 2010
Depression in Partners of Cancer Patients/Nakaya et al
who were aged
30 years at the time of study entry and
resided in Denmark between 1994 and 2003. During the
10 years of follow-up, we identified 42,683 male partners
of women in whom any cancers had been diagnosed. Of
the male partners, a total of 8198 were hospitalized for an
affective disorder. On multivariable analysis, men whose
partners were diagnosed with any cancer were found to be
at an increased risk of being hospitalized with an affective
disorder (multivariate adjusted HR, 1.57; 95% CI, 1.38-
1.79). Thus, we conclude that the results of the current
study may be generalized to the partners of any cancer
patient, and we hypothesize that the partners of patients
with cardiovascular disease and other severe, chronic dis-
orders might also be at an increased risk for affective disor-
ders.40 A further potential limitation in the current study
is lack of information regarding cause of death, which
may have influenced our results. In some elderly people,
death may occur from non-cancer-related, even in those
in whom breast cancer was previously diagnosed. Lastly,
the results of the current study may be due to chance. Our
study was large but included few cases, and we conducted
several statistical analyses; in addition, to our knowledge,
no other studies to date have used hospitalization with
depression as the outcome. Thus, further studies are
needed to confirm the results of the current study.
We conclude that a diagnosis of breast cancer affects
not only the life of the patient but may also seriously affect
their partner. Such interpersonal effects on health chal-
lenge our understanding of cancer as a physical disease,
because it can also have important social and psychologi-
cal effects. We suggest that some type of screening for
depressive symptoms41 in the partners of cancer patients
in general and those of breast cancer patients in particular
might be important for preventing this devastating conse-
quence of cancer.
CONFLICT OF INTEREST DISCLOSURES
Supported by grants from the Japan Society for the Promotion
of Science Postdoctoral Fellowships for Research Abroad (Japan),
the Foundation for Promotion of Cancer Research (Japan) for
the 3rd Term Comprehensive 10-Year Strategy for Control,
Southern Danish University, and the Danish Cancer Society
(Denmark).
REFERENCES
1. Ganz PA. Monitoring the physical health of cancer survivors:
a survivorship-focused medical history. J Clin Oncol. 2006;24:
5105-5111.
2. Mols F, van de Poll-Franse LV, Vingerhoets AJ, et al. Long-
term quality of life among Dutch prostate cancer survivors:
5533
Original Article
results of a population-based study. Cancer. 2006;107:2186-
2196.
3. Holland JC, Reznik I. Pathways for psychosocial care of
cancer survivors. Cancer. 2005;104:2624-2637.
4. Breitbart W, Rosenfeld B, Pessin H, et al. Depression,
hopelessness, and desire for hastened death in terminally ill
patients with cancer. JAMA. 2000;284:2907-2911.
5. Watson M, Haviland JS, Greer S, et al. Influence of psycho-
logical response on survival in breast cancer: a population-
based cohort study. Lancet. 1999;354:1331-1336.
6. Ganz PA, Hahn EE. Implementing a survivorship care plan
for patients with breast cancer. J Clin Oncol. 2008;26:759-
767.
7. House JS, Landis KR, Umberson D. Social relationships
and health. Science. 1988;241:540-545.
8. Berkman LF, Kawachi I. Social Epidemiology. New York:
Oxford University Press; 2000.
9. Sjövall K, Attner B, Lithman T, et al. Influence on the health
of the partner affected by tumor disease in the wife or husband
based on a population-based register study of cancer in
Sweden. J Clin Oncol. 2009;27:4781-4786.
10. Braun M, Mikulincer M, Rydall A, et al. Hidden morbidity in
cancer: spouse caregivers. J Clin Oncol. 2007;25:4829-4834.
11. Langer S, Abrams J, Syrjala K. Caregiver and patient marital
satisfaction and affect following hematopoietic stem cell
transplantation: a prospective, longitudinal investigation.
Psychooncology. 2003;12:239-253.
12. Hagedoorn M, Buunk BP, Kuijer RG, et al. Couples dealing
with cancer: role and gender differences regarding psychologi-
cal distress and quality of life. Psychooncology. 2000;9:232-242.
13. Bishop MM, Beaumont JL, Hahn EA, et al. Late effects of
cancer and hematopoietic stem-cell transplantation on
spouses or partners compared with survivors and survivor-
matched controls. J Clin Oncol. 2007;25:1403-1411.
14. Eton DT, Lepore SJ, Helgeson VS. Psychological distress in
spouses of men treated for early-stage prostate carcinoma.
Cancer. 2005;103:2412-2418.
15. Grunfeld E, Coyle D, Whelan T, et al. Family caregiver
burden: results of a longitudinal study of breast cancer
patients and their principal caregivers. CMAJ. 2004;170:
1795- 1801.
16. Kornblith AB, Herr HW, Ofman US, et al. Quality of life
of patients with prostate cancer and their spouses. The
value of a data base in clinical care. Cancer. 1994;73:2791-
2802.
17. Dalton SO, Steding-Jessen M, Gislum M, et al. Social inequal-
ity and incidence of and survival from cancer in a population-
based study in Denmark, 1994-2003: background, aims, mate-
rial and methods. Eur J Cancer. 2008;44:1938-1949.
18. Official Web site of Denmark. Available at: URL: www.
denmark.dk. Accessed February 5, 2010.
19. Møller S, Jensen MB, Ejlertsen B, et al. Danish Breast
Cancer Cooperative Group. The clinical database and the
treatment guidelines of the Danish Breast Cancer Coopera-
tive Group (DBCG); its 30-years experience and future
promise. Acta Oncol. 2008;47:506-524.
20. Munk-Jørgensen P, Mortensen PB. The Danish Psychiatric
Central Register. Dan Med Bull. 1997;44:82-84.
21. World Health Organization. International Classification of
Diseases. Manual of the International Statistical Classi-
fication of Diseases, Injuries, and Causes of Death. 8th rev.
Geneva: World Health Organization; 1967.
5534
22. World Health Organization. International Statistical Classi-
fication of Diseases and Health Related Problems. Geneva:
World Health Organization; 1992.
23. Eurostat/Statistics Denmark. Statistics on Persons in Denmark.
A Register-Based Statistical System. Brussels, Belgium: Office
for Official Publications of the European Communities; 1995.
24. Thygesen L. The register-based system of demographic and
social statistics in Denmark-an overview. Stat J UN Econ
Commun Eur. 1995;12:49-55.
25. Andersen TF, Madsen M, Jorgensen J, et al. The Danish
National Hospital Register. A valuable source of data for
modern health sciences. Dan Med Bull. 1999;46:263-268.
26. Charlson ME, Pompei P, Ales KL, et al. A new method of
classifying prognostic comorbidity in longitudinal studies:
development and validation. J Chronic Dis. 1987;40:373-383.
27. Hodges LJ, Humphris GM, Macfarlane G. A meta-analytic
investigation of the relationship between the psychological
distress of cancer patients and their careers. Soc Sci Med.
2005;60:1-12.
28. Steptoe A, Wardle J, Pollard TM, et al. Stress, social sup-
port and health-related behavior: a study of smoking, alco-
hol consumption and physical exercise. J Psychosom Res. 1996;
41:171-180.
29. Baumgarten M. The health of persons giving care to the
demented elderly: a critical review of the literature. J Clin
Epidemiol. 1989;42:1137-1148.
30. Grunfeld E, Coyle D, Whelan T, et al. Family caregiver bur-
den: results of a longitudinal study of breast cancer patients
and their principal caregivers. CMAJ. 2004;170:1795-1801.
31. Paskett ED. Breast cancer-related lymphedema: attention to
a significant problem resulting from cancer diagnosis. J Clin
Oncol. 2008;26:5666-5667.
32. Jones LW, Haykowsky M, Peddle CJ, et al. Cardiovascular risk
profile of patients with HER2/neu-positive breast cancer treated
with anthracycline-taxane-containing adjuvant chemotherapy
and/or trastuzumab. Cancer Epidemiol Biomarkers Prev. 2007;16:
1026-1031.
33. Montazeri A. Health-related quality of life in breast cancer
patients: a bibliographic review of the literature from 1974
to 2007. J Exp Clin Cancer Res. 2008;27:32.
34. Carlsen K, Dalton SO, Frederiksen K, et al. Are cancer
survivors at an increased risk for divorce? A Danish cohort
study. Eur J Cancer. 2007;43:2093-2099.
35. Mendes de Leon CF, Kasl SV, Jacobs S. A prospective study of
widowhood and changes in symptoms of depression in a com-
munity sample of the elderly. Psychol Med. 1994;24:613-624.
36. Walach N, Novikov I, Milievskaya I, et al. Cancer among
spouses: review of 195 couples. Cancer. 1998;82:180-185.
37. Dalton SO, Laursen TM, Ross L, et al. Risk for hospitaliza-
tion with depression after a cancer diagnosis: a nationwide,
population-based study of cancer patients in Denmark from
1973 to 2003. J Clin Oncol. 2009;27:1440-1445.
38. Mahoney MC, Bevers T, Linos E, et al. Opportunities and
strategies for breast cancer prevention through risk reduc-
tion. CA Cancer J Clin. 2008;58:347-371.
39. Vink D, Aartsen MJ, Schoevers RA. Risk factors for anxiety and
depression in the elderly: a review. J Affect Disord. 2008;106:29-44.
40. Berg A, Palomäki H, Lönnqvist J, et al. Depression among
caregivers of stroke survivors. Stroke. 2005;36:639-643.
41. Zwahlen D, Hagenbuch N, Carley MI, et al. Screening
cancer patients’ families with the distress thermometer (DT): a
validation study. Psychooncology. 2008;17:959-966.
Cancer December 1, 2010