Abstract

Few studies have examined long-term suicide risk among breast cancer survivors, and there are no data for women in the United States. We quantified suicide risk through 2002 among 723 810 1-year breast cancer survivors diagnosed between January 1, 1953, and December 31, 2001, and reported to 16 population-based cancer registries in the United States and Scandinavia. Among breast cancer survivors, we calculated standardized mortality ratios (SMRs) and excess absolute risks (EARs) compared with the general population, and the probability of suicide. We used Poisson regression likelihood ratio tests to assess heterogeneity in SMRs; all statistical tests were two-sided, with a .05 cutoff for statistical significance. In total 836 breast cancer patients committed suicide (SMR = 1.37, 95% confidence interval [CI] = 1.28 to 1.47; EAR = 4.1 per 100 000 person-years). Although SMRs ranged from 1.25 to 1.53 among registries, with 245 deaths among the sample of US women (SMR = 1.49, 95% CI = 1.32 to 1.70), differences among registries were not statistically significant ( P for heterogeneity = .19). Risk was elevated throughout follow-up, including for 25 or more years after diagnosis (SMR = 1.35, 95% CI = 0.82 to 2.12), and was highest among black women (SMR = 2.88, 95% CI = 1.44 to 5.17) ( P for heterogeneity = .06). Risk increased with increasing stage of breast cancer ( P for heterogeneity = .08) and remained elevated among women diagnosed between 1990 and 2001 (SMR = 1.36, 95% CI = 1.18 to 1.57). The cumulative probability of suicide was 0.20% 30 years after breast cancer diagnosis.

Women with breast cancer account for one in five of all cancer survivors in the United States, numbering approximately 2 million in 2001 ( 1 ) . Given the current 10-year relative survival of 78% ( 2 ) , most patients with breast cancer can expect to live for many years. Nonetheless, a diagnosis of breast cancer has been associated with excess risks of suicide of 30%–50% in Scandinavia ( 35 , 6 ) and Canada ( 7 ) , albeit based on small studies. Suicide risk among patients with breast cancer in the United States has not been evaluated. Further, only a few studies have examined the effect of patient age, race, disease stage, and calendar year on suicide risk or quantified risk 5 years or more after a breast cancer diagnosis ( 3 , 4 , 6 ) . Absolute risk of suicide among patients with breast cancer has not been estimated to date.

We evaluated 723 810 patients diagnosed with a first primary breast cancer between January 1, 1953, and December 31, 2001, who survived at least 1 year and were reported to one of 16 population-based cancer registries in Denmark, Finland, Norway, Sweden, or the United States through the Surveillance, Epidemiology, and End Results (SEER) Program ( 8 , 9 ) . The SEER program areas include Connecticut (from 1973), Hawaii (from 1973), Iowa (from 1973), New Mexico (from 1973), Utah (from 1973), San Francisco-Oakland (from 1973), Detroit (from 1973), Seattle-Puget Sound (from 1974), Atlanta (from 1975), Los Angeles (from 1992), San Jose-Monterey (from 1992), and Alaska (from 1992). Study dates varied according to registry ( Table 1 ). We included a subset of women with extended follow-up, described in previous reports ( 36 ) . Mean follow-up duration starting 1-year after breast cancer diagnosis was 7.7 years (range = <1 month to 49 years).

Table 1.

Standardized mortality ratios (SMRs) and excess absolute risks (EARs) per 100 000 person-years for suicide among 723 810 1-year survivors of breast cancer

Characteristic No. of breast cancer patients  Person-years of follow-up * No. of suicides SMR (95% CI) EAR, No. of suicides per 100 000 person-years 
All patients 723 810 5 598 156 836 1.37 (1.28 to 1.47) 4.1 
Population-based cancer registry      
    US SEER Program (1973–2001) 375 797 2 683 776 245 1.49 (1.32 to 1.70) 3.0 
    Sweden (1958–2001) 153 902 1 334 719 241 1.27 (1.12 to 1.45) 3.9 
    Denmark (1971–1999) 68 045 532 313 166 1.25 (1.07 to 1.46) 6.3 
    Finland (1953–2001) 71 099 570 780 125 1.53 (1.28 to 1.83) 7.6 
    Norway (1961–2000) 54 967 476 569 59 1.40 (1.07 to 1.81) 3.6 
         P for heterogeneity     .19  
Calendar year of breast cancer diagnosis      
    1953–1959 7302 85 951 24 1.86 (1.20 to 2.78) 13.0 
    1960–1969 39 196 479 955 113 1.72 (1.42 to 2.07) 9.9 
    1970–1979 125 136 1 446 762 241 1.31 (1.15 to 1.49) 3.9 
    1980–1989 196 330 1 936 574 267 1.29 (1.15 to 1.46) 3.2 
    1990–2001 355 846 1 648 913 191 1.36 (1.18 to 1.57) 3.1 
         P for heterogeneity     .07  
Race       
    White 672 748 5 280 603 817 1.36 (1.27 to 1.46) 4.1 
    Black 28 406 172 500 11 2.88 (1.44 to 5.17) 4.2 
    Other 22 656 145 053 1.02 (0.44 to 2.01) 0.1 
         P for heterogeneity     .06  
Age at breast cancer diagnosis, y      
    <40 46 275 432 278 63 1.34 (1.04 to 1.73) 3.8 
    40–49 132 397 1 275 941 226 1.42 (1.24 to 1.62) 5.3 
    50–59 163 790 1 400 210 244 1.50 (1.32 to 1.71) 5.8 
    60–69 170 211 1 344 622 176 1.26 (1.09 to 1.47) 2.8 
    ≥70 211 137 1 145 104 127 1.24 (1.04 to 1.48) 2.2 
         P for heterogeneity     .30  
Time since diagnosis, y      
    1 723 810 686 387 116 1.51 (1.25 to 1.82) 5.7 
    2 649 520 607 961 101 1.49 (1.22 to 1.82) 5.5 
    3 573 910 535 855 93 1.57 (1.27 to 1.93) 6.3 
    4 505 066 471 673 68 1.31 (1.02 to 1.66) 3.4 
    5–9 444 626 1 641 357 233 1.30 (1.14 to 1.49) 3.3 
    10–14 236 254 864 229 119 1.28 (1.07 to 1.54) 3.1 
    15–19 123 206 443 981 58 1.25 (0.95 to 1.62) 2.7 
    20–24 61 996 216 155 29 1.32 (0.89 to 1.90) 3.3 
    ≥25 28 053 130 557 19 1.35 (0.82 to 2.12) 3.8 
         P for heterogeneity     .50  
Stage       
    Local 321 395 2 669 382 365 1.38 (1.24 to 1.53) 3.8 
    Regional 187 836 1 259 417 186 1.55 (1.34 to 1.79) 5.3 
    Distant 21 883 67 859 14 2.11 (1.16 to 3.55) 10.9 
    Unknown 38 794 266 779 30 1.05 (0.73 to 1.50) 0.5 
         P for heterogeneity     .08  
Treatment §      
    Surgery only 262 867 2 181 446 280 1.40 (1.24 to 1.58) 3.7 
    Radiotherapy, no chemotherapy 160 281 1 244 520 216 1.46 (1.27 to 1.67) 5.5 
    Chemotherapy, no radiotherapy 64 409 422 011 38 1.12 (0.80 to 1.55) 1.0 
    Radiotherapy and chemotherapy 65 854 322 043 44 1.50 (1.09 to 2.02) 4.6 
    Other/none/unknown 16 497 93 417 17 1.84 (1.14 to 2.96) 8.3 
         P for heterogeneity     .46  
Characteristic No. of breast cancer patients  Person-years of follow-up * No. of suicides SMR (95% CI) EAR, No. of suicides per 100 000 person-years 
All patients 723 810 5 598 156 836 1.37 (1.28 to 1.47) 4.1 
Population-based cancer registry      
    US SEER Program (1973–2001) 375 797 2 683 776 245 1.49 (1.32 to 1.70) 3.0 
    Sweden (1958–2001) 153 902 1 334 719 241 1.27 (1.12 to 1.45) 3.9 
    Denmark (1971–1999) 68 045 532 313 166 1.25 (1.07 to 1.46) 6.3 
    Finland (1953–2001) 71 099 570 780 125 1.53 (1.28 to 1.83) 7.6 
    Norway (1961–2000) 54 967 476 569 59 1.40 (1.07 to 1.81) 3.6 
         P for heterogeneity     .19  
Calendar year of breast cancer diagnosis      
    1953–1959 7302 85 951 24 1.86 (1.20 to 2.78) 13.0 
    1960–1969 39 196 479 955 113 1.72 (1.42 to 2.07) 9.9 
    1970–1979 125 136 1 446 762 241 1.31 (1.15 to 1.49) 3.9 
    1980–1989 196 330 1 936 574 267 1.29 (1.15 to 1.46) 3.2 
    1990–2001 355 846 1 648 913 191 1.36 (1.18 to 1.57) 3.1 
         P for heterogeneity     .07  
Race       
    White 672 748 5 280 603 817 1.36 (1.27 to 1.46) 4.1 
    Black 28 406 172 500 11 2.88 (1.44 to 5.17) 4.2 
    Other 22 656 145 053 1.02 (0.44 to 2.01) 0.1 
         P for heterogeneity     .06  
Age at breast cancer diagnosis, y      
    <40 46 275 432 278 63 1.34 (1.04 to 1.73) 3.8 
    40–49 132 397 1 275 941 226 1.42 (1.24 to 1.62) 5.3 
    50–59 163 790 1 400 210 244 1.50 (1.32 to 1.71) 5.8 
    60–69 170 211 1 344 622 176 1.26 (1.09 to 1.47) 2.8 
    ≥70 211 137 1 145 104 127 1.24 (1.04 to 1.48) 2.2 
         P for heterogeneity     .30  
Time since diagnosis, y      
    1 723 810 686 387 116 1.51 (1.25 to 1.82) 5.7 
    2 649 520 607 961 101 1.49 (1.22 to 1.82) 5.5 
    3 573 910 535 855 93 1.57 (1.27 to 1.93) 6.3 
    4 505 066 471 673 68 1.31 (1.02 to 1.66) 3.4 
    5–9 444 626 1 641 357 233 1.30 (1.14 to 1.49) 3.3 
    10–14 236 254 864 229 119 1.28 (1.07 to 1.54) 3.1 
    15–19 123 206 443 981 58 1.25 (0.95 to 1.62) 2.7 
    20–24 61 996 216 155 29 1.32 (0.89 to 1.90) 3.3 
    ≥25 28 053 130 557 19 1.35 (0.82 to 2.12) 3.8 
         P for heterogeneity     .50  
Stage       
    Local 321 395 2 669 382 365 1.38 (1.24 to 1.53) 3.8 
    Regional 187 836 1 259 417 186 1.55 (1.34 to 1.79) 5.3 
    Distant 21 883 67 859 14 2.11 (1.16 to 3.55) 10.9 
    Unknown 38 794 266 779 30 1.05 (0.73 to 1.50) 0.5 
         P for heterogeneity     .08  
Treatment §      
    Surgery only 262 867 2 181 446 280 1.40 (1.24 to 1.58) 3.7 
    Radiotherapy, no chemotherapy 160 281 1 244 520 216 1.46 (1.27 to 1.67) 5.5 
    Chemotherapy, no radiotherapy 64 409 422 011 38 1.12 (0.80 to 1.55) 1.0 
    Radiotherapy and chemotherapy 65 854 322 043 44 1.50 (1.09 to 2.02) 4.6 
    Other/none/unknown 16 497 93 417 17 1.84 (1.14 to 2.96) 8.3 
         P for heterogeneity     .46  
*

Numbers may not sum to totals because of rounding. SEER = Surveillance, Epidemiology, and End Results.

Because data on race are not collected for patients in Denmark, Sweden, Norway, and Finland, these patients were grouped with the white category, as were patients for whom race was unknown in the SEER Program (n = 1488). Included in the other category were 1345 American Indians–Alaska Natives and 21 311 Asian or Pacific Islanders. Overall rates were used for the non-SEER registries and race-specific rates were used for the SEER registries.

Numbers include only those breast cancer patients reported to registries that collect data on stage (SEER Program, Denmark, Finland, and Norway).

§

Numbers include only those breast cancer patients reported to registries that collect data on initial course of cancer treatment (SEER Program, Denmark, Finland, and Norway); information on subsequent therapy is not available in registry records.

We identified suicide among patients reported to the Scandinavian registries through linkage with the World Health Organization Mortality database for the years 1954–2002 ( 10 ) and suicide among breast cancer patients reported to the SEER registries through mortality data collected and maintained by the National Center for Health Statistics and made available through the SEER program ( 11 ) . Mortality codes for suicide were as follows: E963 and E970–979 (International Classification of Diseases, 7th Revision [ICD-7]), E950–E959 (ICD-8 and ICD-9), and X60–X84 (ICD-10) ( 1215 ) . We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) ( 16 , 17 ) . We multiplied accumulated person-years at risk by suicide rates for each registration area, 5-year age group, and calendar-year interval to calculate the number of expected cases of suicide in each category. To test for heterogeneity in SMRs according to categories of covariates, such as registry, we used standard likelihood ratio tests that compared Poisson regression models, which included the covariate, with a simple model without the covariate ( 18 ) . We also used likelihood ratio tests to evaluate the statistical significance of the following interactions: 1) calendar year and time since breast cancer diagnosis and type of treatment and 2) age and time since breast cancer diagnosis, stage, and type of treatment. We compared models with main effects for the two variables plus an interaction term to simpler models that included only main effects. All tests were two-sided, with a .05 cutoff for statistical significance ( 18 ) . We also quantified the excess absolute risk (EAR) of suicide among patients with breast cancer compared with the background population ([number of observed cases – number of expected cases) × 100 000 person-years) and the crude probability of suicide among patients with breast cancer by use of a competing risk model ( 19 ) . Because suicide deaths could be miscoded as accidents ( 3 , 20 ) , we also examined mortality attributed to accidents and to other external causes.

In this cohort, 836 patients with breast cancer committed suicide (SMR = 1.37, 95% CI = 1.28 to 1.47; EAR = 4.1 per 100 000 person-years) ( Table 1 ). SMRs were lowest in Denmark (SMR = 1.25, 95% CI = 1.07 to 1.46) and Sweden (SMR = 1.27, 95% CI = 1.12 to 1.45) and highest in the United States, with 245 deaths in the US cohort (SMR = 1.49, 95% CI = 1.32 to 1.70), and in Finland (SMR = 1.53, 95% CI = 1.28 to 1.83), but differences across registries were not statistically significant ( P for heterogeneity = .19) ( Table 1 ). EARs were highest for Finland (EAR = 7.6 per 100 000 person-years) and Denmark (EAR = 6.3 per 100 000 person-years) and lowest for the United States (EAR = 3.0 per 100 000 person-years). The SMRs and corresponding EARs are not parallel because of variation in background suicide rates among countries ( 10 , 11 , 21 ) . Elevated SMRs were observed for all calendar-year periods, including for women diagnosed between 1990 and 2001 (SMR = 1.36, 95% CI = 1.18 to 1.57), but were slightly higher among those diagnosed before 1970 ( P for heterogeneity = .07). SMRs varied by race, with risk higher in black women (SMR = 2.88, 95% CI = 1.44 to 5.17) than white women (SMR = 1.36, 95% CI = 1.27 to 1.46) and other races (SMR = 1.02, 95% CI = 0.44 to 2.01) ( P for heterogeneity = .06). EARs, however, were similar in black women and white women. Slight variations in risk according to age at breast cancer diagnosis were not statistically significant. Elevated SMRs were evident throughout the follow-up period, including for 25 or more years after diagnosis (SMR = 1.35, 95% CI = 0.82 to 2.12), but were slightly, but not statistically significantly, higher in the initial years after diagnosis. Risk increased with increasing stage of breast cancer ( P for heterogeneity = .08); all suicides among women with distant disease occurred among white women. Small differences in risk according to initial treatment were not statistically significant. Analyses based on type of breast cancer surgery, which was available for US women (1983–2001), showed little difference in SMRs among women who received breast-conserving surgery (SMR = 1.22, 95% CI = 0.89 to 1.64) or radical mastectomy (SMR = 1.30, 95% CI = 1.04 to 1.63) (data not shown in table). None of the interactions between covariates that we evaluated was statistically significant. Cumulative probabilities of suicide 5, 10, 20, and 30 years after breast cancer diagnosis were 0.05% (95% CI = 0.04% to 0.06%), 0.10% (95% CI = 0.09% to 0.11%), 0.16% (95% CI = 0.15% to 0.17%), and 0.20% (95% CI = 0.18% to 0.22%), respectively. The SMR for accidents and other external causes of death was 0.95 (95% CI = 0.93 to 0.99).

This study is the largest population-based investigation to date of suicide after a breast cancer diagnosis and the first analytic study of US women. New findings include the persistence of elevated suicide risk than 25 or more years after breast cancer diagnosis, with a slight diminution in risk among patients diagnosed after 1969 compared with earlier periods, perhaps because of improved treatments ( 4 ) ; a statistically significant 50% increase in suicide among US women; increasing suicide risk with increasing breast cancer stage; and higher risk in black women than white women and women of other races.

Although most patients with breast cancer appear to adapt well, a minority suffer from significant psychosocial distress ( 22 ) . Estimates of the prevalence of clinical depression or depressive symptoms in patients with breast cancer vary greatly, ranging from 1.5% to 46% ( 23 ) . Importantly, psychosocial factors (including depression) and use of antidepressant medications do not appear to be risk factors for the development of breast cancer ( 24 , 25 ) . Depression, however, was an important predictor of late-stage breast cancer diagnosis in one study ( 26 ) but not in another ( 27 ) . A Danish investigation ( 3 ) that included a subset of our population found no association between suicide and stage at breast cancer diagnosis. However, in our analysis an association with stage was evident in the extended Danish cohort and overall. We did not have information on depression, but our results are consistent with reports of increased risks of hospitalization for affective disorders and anxiety in patients with breast cancer compared with the general population ( 20 ) .

Our findings should be considered in light of the strengths and limitations of cancer registry and mortality data. Population-based investigations circumvent the selection bias in clinical or hospital studies and permit evaluation of mortality among a large number of patients. Possible limitations include the problem of accurate ascertainment of suicide, which tends to be underreported as a cause of death ( 28 ) , possibly more so in cancer patients than in the general population ( 3 , 4 , 6 , 29 ) . Notably, mortality from accidents and other external causes was not elevated in our analysis. Ascertainment of suicide also varies according to certification procedures ( 28 ) , but all analyses were controlled for country and calendar year to take into account reporting differences ( 21 ) . We also lacked information on possible confounding factors, notably marital status and socioeconomic status. Because unmarried women have higher rates of suicide ( 28 ) and breast cancer ( 30 ) , adjustment for this variable might attenuate our observed risk estimates. In contrast, adjustment for socioeconomic status would likely make little difference because socioeconomic status is directly associated with breast cancer risk ( 30 ) but is not clearly associated with female suicide risk ( 31 , 32 ) .

Nonetheless, our international, population-based study highlights a small, but statistically significant, increased long-term risk of suicide after a breast cancer diagnosis. In contrast, suicide risk for most cancers decreases to expected levels several years after diagnosis ( 6 ). This difference may reflect the unique chronic and indolent nature of breast cancer with recurrences possible many years after diagnosis. Thus, although the cumulative probability of suicide is small, our results suggest that long-term follow-up programs for breast cancer survivors should include resources devoted to psychosocial concerns.

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The authors had full responsibility for the following activities: design of the study, the collection of the data, the analysis and interpretation of the data, the decision to submit the manuscript for publication, and the writing of the manuscript.
The authors are indebted to Jeremy Miller of Information Management Services, Inc, for computer support.

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