Depression and Long-term Mortality among 5-year Breast Cancer Survivors in Korea: A Population-based Cohort Study

doi:10.21203/rs.3.rs-3991118/v1

Download PDF

Research Article

Depression and Long-term Mortality among 5-year Breast Cancer Survivors in Korea: A Population-based Cohort Study

https://doi.org/10.21203/rs.3.rs-3991118/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Depression is common and harmful among breast cancer survivors, but it may be neglected and untreated in non-Western settings. We examined the association of depression after breast cancer diagnosis with long-term mortality risk in a Korean cohort.

Methods

We used data from the National Health Insurance Service cancer patients cohort database of South Korea. We included women aged 40 or older who were diagnosed with breast cancer between 2007 and 2013, survived at least 5 years, and had no depression history. Depression was defined as hospitalization for more than 2 days due to depression (ICD-10 code F22 or F23) after diagnosis. We assessed all-cause, cancer-specific, and non-cancer-specific mortality by Cox proportional hazards model, adjusting for covariates.

Results

Among 30,371 women (mean [SD] age, 56.5 [11.4] years), 30,371 had depression. During the 5-year period, 1,904 deaths occurred (33.6 per 1,000 person-years). Depression patients had higher risks of all-cause mortality (adjusted hazard ratio [aHR], 1.38; 95% CI, 1.03–1.86) and non-cancer-specific mortality (aHR, 1.81; 95% CI, 1.14–2.86) compared to non-depression patients with Charlson comorbidity index of 2 or more. Cancer mortality was not significantly different. All-cause mortality was also higher for depression patients aged 65 or older (aHR, 1.96; 95% CI, 1.27–3.03).

Conclusions

Depression was linked to increased mortality among 5-year breast cancer survivors, especially for non-cancer causes. This study implies the need for depression screening and treatment among breast cancer patients, especially in non-Western settings where depression may be underdiagnosed and undertreated.

breast cancer

depression

mortality

cohort study

South Korea

Women with breast cancer have to cope with many difficulties that affect their quality of life in both psychological and physical aspects, as they face various sources of stress, fear, and emotional distress related to their condition, treatment options, and outcomes.[1, 2] Depression is one of the most common mental health problems among breast cancer patients, affecting up to 40% of them at some point during or after their treatment.[3] Depression can have negative impacts on the quality of life, adherence to treatment, and survival outcomes of breast cancer patients.[4–6] The mechanisms by which depression influences breast cancer survival are complex and multifactorial, involving both behavioral and biological pathways.[7, 8] Depression has been associated with impaired immune function, increased inflammation, changes in hormonal levels, and the potential to impact cytokine homeostasis, consequently enhancing angiogenesis and metastasis.[9, 10] Moreover, depression may reduce the likelihood of receiving guideline-recommended treatment, which can affect survival.[8]

Substantial evidence gathered from observational and clinical studies strongly indicates a link between the simultaneous occurrence of depression and poorer survival outcomes among women diagnosed with breast cancer, as noted across short- and long-term follow-ups.[5, 11, 12] However, previous research has presented conflicting outcomes regarding the connection between depression and survival in breast cancer. Some observational studies have even suggested the absence of a significant relationship between depression and mortality.[13, 14] Moreover, most of these studies have primarily centered on Western populations, potentially differing in depression prevalence and treatment approaches from other regions, with Asian countries showing similar rates but notably higher rates in Turkey (46%), South Africa, Mexico (43%), and Nigeria (40.3%), utilizing various assessment methods.[6] Consequently, uncertainty remains regarding any definitive association between depression and the progression or mortality rates related to breast cancer.

To address this evidence gap, we investigated the association between depression occurrences following breast cancer diagnosis and death from all causes, non-cancer causes, and cancer-related deaths using a population-based study involving 5-year breast cancer survivors in Korea.

Data Source

The study, conducted as a retrospective cohort study, utilized the National Health Insurance Service (NHIS-2023-1-289) cancer patients cohort database in South Korea, spanning from January 1st, 2006, to December 31st, 2022.[15] South Korea's national healthcare system allows for the utilization of healthcare data from a majority of the population for research purposes. The NHIS has systematically collected health screening information for Koreans, encompassing age, gender, insurance grade (as a substitute for income), residential region details, health examination dates, medical practice history, prescription data, dental treatment status, oriental medicine treatment, and disease history diagnosed with ICD-10 codes [16], which represents the 10th revision of the International Statistical Classification of Diseases. Health checkups are regularly conducted by the NHIS for adults over 40 years old every two years. Utilizing this data allows for the determination of various factors, including patients' smoking status, alcohol consumption, weekly physical activity frequency, blood pressure, total cholesterol, body mass index, and more.[16]

Study Population and Design

The NHIS cancer patients cohort database covers the years 2006 to 2022. However, we excluded a group of patients who underwent breast cancer treatment between January 1st, 2006, and December 31st, 2006, as our focus was on individuals newly diagnosed with breast cancer. In Fig. 1, we initially identified 63,014 cancer patients who received a new breast cancer diagnosis between January 1st, 2007, and December 31st, 2013, and survived for at least 5 years. Among them, 27,471 patients lacked available measurements for body mass index, total cholesterol, and blood pressure, leading to their exclusion. Additionally, 4,256 patients had unusable age and sex data and were therefore excluded.

To define newly diagnosed depression, we excluded 134 patients with a recorded history of depression before their newly diagnosed breast cancer date and further excluded 161 male patients. Consequently, the remaining cohort consisted of 30,873 individuals who were newly diagnosed with breast cancer between 2007 and 2013, survived for at least 5 years post-diagnosis, and had no history of depression before their breast cancer diagnosis date. This study was carried out with the approval of the Institutional Review Board of Seoul National University Hospital (IRB number: E-2204-038-1314).

Key variables

We identified breast cancer patients using the ICD-10 code (C50) and individuals with depression through ICD-10 codes (F32, F33).[17] The variables under investigation included body mass index, blood pressure, fasting serum glucose, and total cholesterol. Covariate data encompassed sex, age, income level, drinking frequency or quantity, physical activity frequency, smoking habits, and Charlson Comorbidity Index (CCI). The frequency of moderate-intensity exercise was calculated as the sum of physical activity instances lasting more than twenty minutes per week and those lasting more than thirty minutes per week.

For the definition of depression patients, we considered individuals hospitalized for at least 2 days due to depression (ICD-10 code; F22, F23)[17] during the 5-year survivor duration, corresponding to the 5-year follow-up period after the date of newly diagnosed breast cancer. Patients experiencing all-cause death, cancer-cause death, and non-cancer cause death were categorized as those who had passed away from the end date of the 5-year survivor duration until December 31st, 2021.

Statistical analysis

Following the diagnosis of breast cancer, characteristics of patients who survived for at least 5 years were categorized based on their history of depression during the survivor period. Continuous variables exhibiting a normal distribution were presented using standard deviation and average, while dichotomous and categorical data were summarized using frequency and ratio. Comparative analyses of clinical characteristics between breast cancer patients in the non-depression and depression groups involved chi-square tests for categorical and dichotomous variables, and independent sample t-tests for normally distributed continuous variables.

Cox proportional hazards regression models were utilized in the comprehensive analysis, accounting for possible covariates.[18] The final results were analyzed after accounting for patients' personal information (such as sex, age, and income) and health examination data (including smoking habits and frequency, blood pressure, Charlson Comorbidity Index, alcohol frequency and quantity, body mass index [BMI], total cholesterol, fasting serum glucose). The study assessed all-cause mortality, cancer-related mortality, and non-cancer-related mortality, analyzing the incidence of death in the two groups of breast cancer patients over person-years of follow-up. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated to interpret the results,[19] considering a P value below 0.05 as indicative of statistical significance. Subjects with missing values were excluded before the analysis, and SAS Enterprise Guide version 7.1 was utilized.

Baseline Characteristics

Table 1 presents the demographic characteristics of a cohort comprising 30,371 patients diagnosed with new-onset depression and 502 patients without a history of depression during the 5-year survival period following a new breast cancer diagnosis. The study exclusively includes female subjects, with an average age of 56.5 years for both groups. Analysis of household income, based on NHIS premium data, revealed that the highest income bracket was predominant in both groups, encompassing 11,296 patients (37.2%) with depression and 169 patients (33.7%) without depression. Regarding BMI, the average value was 23.5 for both groups. Blood pressure parameters, including systolic and diastolic readings, were higher among patients with depression. Total cholesterol levels were elevated in the non-depressed group, averaging 194.1, whereas fasting blood sugar levels were higher in the group experiencing new depression, with an average value of 97.7. Examining lifestyle factors within the two-year survival period after a five-year breast cancer diagnosis, over 94% of individuals in both groups reported being non-smokers, and more than 88% indicated abstaining from alcohol consumption weekly. In terms of exercise frequency, over half of the participants reported not exercising weekly, while more than 10% in each group engaged in physical activity 1–2 times, 3–4 times, or 5 times per week. The CCI revealed that most individuals in both groups had a score of 1 or higher, indicating the presence of comorbidities.

Table 1

Descriptive statistics of the participants in the National Health Insurance Service.
	Patients who have not been diagnosed with depression since breast cancer diagnosis	New depression diagnostic patients after breast cancer diagnosis	p value
	(n = 30,371)	(n = 502)	p value
Age, years, mean (SD)	56.5 (9.7)	56.5 (9.0)	0.018
Household income^a, n (%)			0.267
First (highest)	11,296 (37.2)	169 (33.7)
Second	7,180 (23.6)	135 (26.9)
Third	5,646 (18.6)	92 (18.3)
Fourth (lowest)	6,249 (20.6)	106 (21.1)
Body mass index, kg/m²	23.5 (3.3)	23.5 (3.1)	0.095
Systolic blood pressure, mmHg	121.1 (15.1)	118.7 (15.2)	0.839
Diastolic blood pressure, mmHg	74.4 (9.8)	74.3 (9.9)	0.590
Total cholesterol, mg/dL	192.5 (36.7)	194.1 (35.6)	0.348
Fasting serum glucose, mg/dL	97.7 (20.2)	97.4 (18.7)	0.020
Cigarette smoking, n (%)			0.004
Never smoker	29,372 (96.7)	473 (94.2)
Past smoker	636 (2.1)	21 (4.2)
Current smoker	363 (1.2)	8 (1.6)
Alcohol consumption, n (%)			0.042
None	27,038 (89.0)	444 (88.5)
1–2 times/week	2,947 (9.7)	51 (10.2)
3–4 times/week	287 (0.9)	7 (1.4)
≥5 times/week	99 (0.3)	0 (0.0)
Physical activity, n (%)			0.844
None	17,295 (57.0)	291 (58.1)
1–2 times/week	4,799 (15.8)	82 (16.4)
3–4 times/week	3,934 (13.0)	63 (12.6)
≥5 times/week	4,326 (14.3)	65 (13.0)
Charlson comorbidity index, n (%)			< .0001
0	971 (3.2)	3 (0.6)
1	14,792 (48.7)	164 (32.7)
≥2	14,608 (48.1)	335 (66.7)
Data are presented as median (interquartile range) unless otherwise specified.
^aProxy for socioeconomic status based on the insurance premium of the National Health Insurance Service.

Depression in survivor period and mortality Outcomes among 5-year survivors breast cancer patients

Table 2 presents the primary outcome investigated in this study, focusing on the diagnosis of new-onset depression during the 5-year survival period for individuals following a new breast cancer diagnosis. The analysis utilized a multivariable Cox proportional hazard regression model. Model 1 adjusted for age only, while Model 2 incorporated adjustments for both age and household income. Model 3 was further adjusted for patient information, including age, household income, smoking status, alcohol consumption, and physical activity. Finally, Model 4 encompassed comprehensive adjustments for all patient information, such as age, physical activity, body mass index, diagnostic blood pressure, fasting serum glucose, total cholesterol, and CCI. According to the findings from Model 4, the mortality rate for overall causes of death increased by 1.38 times for patients diagnosed with depression during the 5-year survival period (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.03–1.86, p < 0.05), signifying a statistically significant result. Although the mortality rate related to cancer exhibited a similar trend, it did not reach statistical significance. Conversely, for mortality attributed to reasons other than cancer, the group of patients diagnosed with depression showed a significant increase by 1.81 times (aHR 1.81, 95% CI 1.14–2.86, p < 0.05).

Table 2

HRs of all-cause mortality, cancer-cause mortality and no cancer-cause mortality by diagnosed with depression after newly diagnosed with breast cancer.
			HR (95% CI)
	Event, n	Per 1,000 person-y	Model 1	Model 2	Model 3	Model 4
All-cause mortality
Patients who have not been diagnosed with depression since breast cancer diagnosis (n = 30,371)	1,859	183436	1.00 (Ref.)	1.00 (Ref.)	1.00 (Ref.)	1.00 (Ref.)
New depression diagnostic patients after breast cancer diagnosis (n = 542)	45	2837	1.61 (1.20–2.17)**	1.61 (1.19–2.16)**	1.57 (1.17–2.12)**	1.38 (1.03–1.86)*
Cancer-cause mortality
Patients who have not been diagnosed with depression since breast cancer diagnosis (n = 26,616)	1,146	183436	1.00 (Ref.)	1.00 (Ref.)	1.00 (Ref.)	1.00 (Ref.)
New depression diagnostic patients after breast cancer diagnosis (n = 542)	26	2837	1.48 (1.00-2.18)*	1.47 (1.00-2.17)	1.45 (0.98–2.14)	1.20 (0.81–1.77)
No cancer-cause mortality
Patients who have not been diagnosed with depression since breast cancer diagnosis (n = 26,616)	713	183436	1.00 (Ref.)	1.00 (Ref.)	1.00 (Ref.)	1.00 (Ref.)
New depression diagnostic patients after breast cancer diagnosis (n = 542)	19	2837	1.81 (1.15–2.86)*	1.80 (1.14–2.84)*	1.76 (1.12–2.78)*	1.81 (1.14–2.86)*
CI = confidence interval, HR = hazard rstio, Crude HR, relative hazard ratio.
*Incidence rate, per 1000 person-year
Model 1: adjusted for age.
Model 2: adjusted for age and household income.
Model 3: adjusted for age, household income, smoking status, alcohol consumption and physical activity.
Model 4: adjusted for age, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diastolic blood pressure, fasting serum glucose, total cholesterol, and Charlson comorbidity index.
p < 0.05, p < 0.01, **p < 0.001

Table 3. Stratified analysis of the association between diagnosed with depression during the survivor period among breast cancer and risk of all-cause mortality according to age, income, physical activity, drink habits, and smoking status.
	Patients who have not been diagnosed with depression since breast cancer diagnosis	New depression diagnostic patients after breast cancer diagnosis		Patients who have not been diagnosed with depression since breast cancer diagnosis	New depression diagnostic patients after breast cancer diagnosis
Age < 65	24,079	421	Age ≥ 65	6,292	81
Events, n	1,053	24	Events, n	806	21
Per 1,000 person-y	146807	2396	Person-years	36628	441
aHR (95% CI)	1.00 (Ref.)	1.13 (0.75–1.69)	aHR (95% CI)	1.00 (Ref.)	1.96 (1.27–3.03)**
Income higher		18,476	304	Income lower	11,895	198
Events, n		1,169	24	Events, n	690	21
Per 1,000 person-y		112189	1684	Person-years	71246	1152
aHR (95% CI)		1.00 (Ref.)	1.23 (0.82–1.85)	aHR (95% CI)	1.00 (Ref.)	1.57 (1.02–2.43)*
Physical activity higher		13,059	210	No physical activity	17,295	291
Events, n		683	12	Events, n	1,176	33
Per 1,000 person-y		78437	1158	Person-years	104876	1672
aHR (95% CI)		1.00 (Ref.)	1.01 (0.57–1.78)	aHR (95% CI)	1.00 (Ref.)	1.59 (1.12–2.25)**
No drink		27,038	444	Drink higher	3,333	584
Events, n		1,749	41	Events, n	110	41
Per 1,000 person-y		163322	2498	Person-years	20114	339
aHR (95% CI)		1.00 (Ref.)	1.36 (0.99–1.85)	aHR (95% CI)	1.00 (Ref.)	1.87 (0.68–5.13)
No smoking		29,372	473	Smoking higher	999	29
Events, n		1,790	41	Events, n	69	4
Per 1,000 person-y		177552	2676	Person-years	5883	161
aHR (95% CI)		1.00 (Ref.)	1.35 (0.99–1.83)	aHR (95% CI)	1.00 (Ref.)	2.28 (0.82–6.37)
Charlson comorbidity index < 2		15,763	167	Charlson comorbidity index ≥ 2	14,608	335
Events, n		475	8	Events, n	1,384	37
Per 1,000 person-y		94893	934	Per 1,000 person-y	88542	1903
aHR (95% CI)		1.00 (Ref.)	1.83 (0.91–3.69)	aHR (95% CI)	1.00 (Ref.)	1.33 (0.96–1.84)
CI = confidence interval, HR = hazard ratio, Crude HR, relative hazard ratio ,aHR = adjusted hazard ratio. Charlson comorbidity index information is the set at the time of new breast cancer diagnosis.
Hazard ratios calculated by Cox proportional hazards regression analysis: adjusted for adjusted for age, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diastolic blood pressure, fasting serum glucose, total cholesterol, and Charlson comorbidity index. p < 0.05, p < 0.01, **p < 0.001

Stratified analysis

For the three stratified analyses involving mortality (all-cause, cancer-cause, and non-cancer-cause), the study divided participants into groups based on the CCI (< 2, ≥ 2), age (< 65, ≥ 65), income (< 50%, ≥ 50%), physical activity (exercise or no exercise), drink habits (non-drinker or drinker), and smoking status (non-smoker or smoker). The same correction variables as those in Model 4 from Table 2 were applied. In summary, the stratified analysis in Table 3 indicated that for all-cause mortality, a history of depression was statistically significant in patients aged 65 and older, those with lower income, and those who did not engage in physical activity. Additionally, for cancer-cause mortality, a statistically significant association with a history of depression was observed in patients aged 65 and older. For non-cancer-cause mortality, a history of depression was statistically significant in patients with a CCI of less than 2, those aged 65 and older, those with lower income, those who did not engage in physical activity, and those with higher alcohol consumption. Stratified analyses of the association between depression diagnosis during the survivor period and the risk of cancer or non-cancer mortality are presented in Tables S1 to S2 for breast cancer patients, by age, income, physical activity, drink habits, and smoking status.

This longitudinal study conducted on a population basis demonstrated a notable association between post-breast cancer diagnosis depression and extended-term mortality among 5-year cancer survivors (CS). Notably, this research is the initial one to illustrate that depression subsequent to a breast cancer diagnosis is correlated with a heightened probability of mortality, especially non-cancer-related mortality, among 5-year CS in Korea.

Our finding of a significant association between post-breast cancer depression and increased mortality among 5-year cancer survivors is in line with previous evidence on the adverse impact of depression on cancer prognosis. A meta-analysis of 31 prospective studies found a 25% higher mortality rate among cancer patients experiencing depressive symptoms and a 39% increased mortality rate in individuals diagnosed with major depression, even after accounting for prognostic factors.[22] However, these meta-analyses faced limitations due to significant heterogeneity stemming from different cancer types.[23] Additionally, considering breast cancer's hormone-dependent nature, its reaction to mental health conditions might differ from that of other cancers.[5] A systematic analysis of 17 studies involving 282,203 breast cancer patients revealed that depression was linked to cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)].[5] However, most of these studies were conducted in Western countries, and few studies have examined the effect of depression on non-cancer-related mortality in breast cancer survivors. Our study is the first to demonstrate that depression after a breast cancer diagnosis is associated with a higher risk of non-cancer-related mortality among 5-year cancer survivors in Korea.

Currently, evidence on the association between depression and breast cancer mortality is limited to observational and genetic studies. One study in the UK Biobank cohort found that post-diagnostic use of selective serotonin reuptake inhibitors (SSRIs), a common antidepressant medication, was associated with a 27% increase in breast cancer mortality, but this association was largely attenuated when restricting to patients with prior depression or comparing to other antidepressant medications.[24] This study suggested a possible causal relationship between depression and breast cancer mortality, but also highlighted the potential confounding by indication. A randomized trial involving 125 women with metastatic breast cancer (MBC) revealed cortisol dysregulation in MBC patients compared to controls, predicting shorter survival.[8] This study suggests that irregular cortisol patterns in both MBC and depression may indicate an inadequate response to inflammation related to cancer. By disrupting cortisol regulation, tumors using inflammatory mediators may cause resistance to glucocorticoids, but addressing depression could potentially break this cycle, relieving related symptoms.[25] While these studies have demonstrated a biological link between depression and breast cancer mortality, but the evidence is limited to specific regions of the North American and European populations. Shim et al. (2020) discovered that depression and anxiety disorders, as studied using Korean NHIS data, heightened the risk of breast cancer mortality, particularly non-cancer-related death, and that antidepressant treatment attenuated the risk. Moreover, this effect was independent of sociodemographic and clinical factors.[26]

Depression may increase non-cancer-related deaths after breast cancer diagnosis through various biological mechanisms, such as metabolic, immuno-inflammatory, autonomic and hypothalamic-pituitary-adrenal (HPA)-axis dysregulations.[27] Breast cancer patients who have negative coping styles may suffer from chronic stress-induced immune dysregulation, impairing the body’s ability to cope with stress, infections, and chronic diseases, thereby resulting in increased morbidity and mortality.[28] Psychiatric patients with physical ailments might experience higher non-cancer-related mortality and reduced specificity in cancer-related issues owing to inadequate adherence to treatments and unhealthy behaviors.[29, 30] In Korea, where cancer is the leading cause of death, depression and anxiety are common among breast cancer patients and survivors, but often underdiagnosed and undertreated.[31] The Korean health system provides universal coverage for cancer treatment, but the access to and quality of mental health care and support systems for health and social welfare are still inadequate.[32, 33] Our study of the Korean cohort further extends evidence on the long-term mortality impact of post-breast cancer diagnosis depression among 5-year cancer survivors, highlighting the need for screening and treating depression in breast cancer patients, especially in Asian populations where depression may be overlooked and undertreated.

The strengths of our study stand out, which encompassed analyses of a large and representative study population linked to the Korean NHIS and death registry data to capture not only the diagnosis of depression and health service utilization, but also the cause and date of death. Moreover, we were able to address a diverse set of confounders for sociodemographic factors, health status, health behavior, comorbidities, and clinical characteristics for adjustment and stratified analyses to minimize potential bias in the analyses.

Limitations

Our study has several limitations. First, we did not have information on the type and duration of antidepressant medication used by the breast cancer survivors with depression. Instead, we only used the diagnosis of depression from the NHIS database as an indicator of antidepressant use. Nonetheless, previous studies have shown that antidepressant medication can reduce the risk of mortality in breast cancer patients with depression. Second, we did not account for the severity of the disease, duration since diagnosis, and the specific treatment undergone by the women with breast cancer. These variables also affect the depression levels of these patients. [34] Thus, the validity of our findings is limited by these confounding factors. However, we tried to reduce the effect of deaths caused by this factor by selecting only 5-year survivors for our study. A meta-analysis of 76 prospective studies with 105 samples showed that depression’s impact on mortality is independent of the disease stage in cancer patients.[35] Third, it should be noted that our study measured depression only once at the baseline. Therefore, whether the breast cancer survivors in our cohort had persistent or recurrent depression during the follow-up period remains unknown. Nonetheless, our results showed a significant association between depression and mortality, especially non-cancer-related mortality, in breast cancer survivors. This finding is consistent with previous studies that reported a higher risk of death from cardiovascular diseases, respiratory diseases, and suicide in breast cancer patients with depression.

In conclusion, our study of the Korean cohort showed that depression after breast cancer diagnosis increased the long-term mortality risk among 5-year survivors, underscoring the need for screening and treating depression to improve survival in this population. However, since this is an observational study, further research is needed to determine the exact impact of depression and its treatment on breast cancer outcomes, especially in Asian settings where depression may be overlooked and undertreated.

Data availability

The study findings are supported by data from the Korea NHIS, but access to these data is restricted and used under license for this current study, thus not publicly accessible.

Author Contributions:

SMP had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: SKL, SP, and SMP

Acquisition, analysis, or interpretation of data: SKL, SP, and SMP

Drafting of the manuscript: SKL and SP

Critical review of the manuscript for important intellectual content: SKL, SP, and SMP Statistical analysis: SKL and SP

Obtained funding: SKL and SP

Administrative, technical, or material support: SKL and SP

Supervision: SMP

Funding: The Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(RS-2023-00244084); Sangwoo Park received a BK21 FOUR education program scholarship. It was offered by the National Research Foundation of Korea(2021R1F1A1063346).

Conflicts of interest

The authors declare no potential conflicts of interest.

Iddrisu, M., L. Aziato, and F. Dedey, Psychological and physical effects of breast cancer diagnosis and treatment on young Ghanaian women: a qualitative study. BMC Psychiatry, 2020. 20(1): p. 353.
İzci, F., et al., Psychiatric Symptoms and Psychosocial Problems in Patients with Breast Cancer. J Breast Health, 2016. 12(3): p. 94-101.
Chen, L., et al., Global trends of research on depression in breast cancer: A bibliometric study based on VOSviewer. Front Psychol, 2022. 13: p. 969679.
Fann, J.R., et al., Major depression after breast cancer: a review of epidemiology and treatment. General Hospital Psychiatry, 2008. 30(2): p. 112-126.
Wang, X., et al., Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients. Molecular Psychiatry, 2020. 25(12): p. 3186-3197.
Javan Biparva, A., et al., Global depression in breast cancer patients: Systematic review and meta-analysis. PLoS One, 2023. 18(7): p. e0287372.
Smith, H.R., Depression in cancer patients: Pathogenesis, implications and treatment (Review). Oncol Lett, 2015. 9(4): p. 1509-1514.
Giese-Davis, J., et al., Decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer: a secondary analysis. J Clin Oncol, 2011. 29(4): p. 413-20.
Bortolato, B., et al., Depression in cancer: The many biobehavioral pathways driving tumor progression. Cancer Treat Rev, 2017. 52: p. 58-70.
Cañas-González, B., et al., Influence of Stress and Depression on the Immune System in Patients Evaluated in an Anti-aging Unit. Front Psychol, 2020. 11: p. 1844.
Vodermaier, A., et al., Prospective associations of depression with survival: a population-based cohort study in patients with newly diagnosed breast cancer. Breast Cancer Res Treat, 2014. 143(2): p. 373-84.
Kanani, R., et al., The association of mood disorders with breast cancer survival: an investigation of linked cancer registration and hospital admission data for South East England. Psychooncology, 2016. 25(1): p. 19-27.
Kim, S.Y., M. Jhon, and D.W. Kissane, Adverse impact of depression and anxiety on mortality in patients with breast cancer. Transl Cancer Res, 2020. 9(7): p. 4046-4051.
Jamison, R.N., T.G. Burish, and K.A. Wallston, Psychogenic factors in predicting survival of breast cancer patients. J Clin Oncol, 1987. 5(5): p. 768-72.
Seong, S.C., et al., Cohort profile: the national health insurance service-national health screening cohort (NHIS-HEALS) in Korea. BMJ open, 2017. 7(9): p. e016640.
Choi, D., et al., Impact of discrepancies in general and abdominal obesity on major adverse cardiac events. Journal of the American Heart Association, 2019. 8(18): p. e013471.
Choi, S., K. Lee, and S.M. Park, Combined Associations of Changes in Noncombustible Nicotine or Tobacco Product and Combustible Cigarette Use Habits With Subsequent Short-Term Cardiovascular Disease Risk Among South Korean Men: A Nationwide Cohort Study. Circulation, 2021. 144(19): p. 1528-1538.
Di Ciaula, A., et al., Cholecystectomy and risk of metabolic syndrome. European journal of internal medicine, 2018. 53: p. 3-11.
Fairfield, C.J., S.J. Wigmore, and E.M. Harrison, Gallstone disease and the risk of cardiovascular disease. Scientific reports, 2019. 9(1): p. 1-8.
Hwang, S.E., et al., Association between social trust and the risk of cardiovascular disease in older adults in Korea: a nationwide retrospective cohort study. BMC Public Health, 2020. 20(1): p. 1844.
Kim, Y.J., et al., Risk of Heart Disease after Cholecystectomy: A Nationwide Population-Based Cohort Study in South Korea. Journal of Clinical Medicine, 2021. 10(15): p. 3253.
Satin, J.R., W. Linden, and M.J. Phillips, Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer, 2009. 115(22): p. 5349-61.
Urbach, D., et al., Cancer heterogeneity: origins and implications for genetic association studies. Trends Genet, 2012. 28(11): p. 538-43.
Busby, J., et al., Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study. Breast Cancer Research, 2018. 20(1): p. 4.
Andersen, B.L., et al., Distress reduction from a psychological intervention contributes to improved health for cancer patients. Brain Behav Immun, 2007. 21(7): p. 953-61.
Shim, E.J., et al., Association of depression and anxiety disorder with the risk of mortality in breast cancer: A National Health Insurance Service study in Korea. Breast Cancer Res Treat, 2020. 179(2): p. 491-498.
Young, K. and G. Singh, Biological Mechanisms of Cancer-Induced Depression. Front Psychiatry, 2018. 9: p. 299.
Chen, X., et al., Chronic stress-induced immune dysregulation in breast cancer: Implications of psychosocial factors. J Transl Int Med, 2023. 11(3): p. 226-233.
Ko, A., et al., Association of pre-existing depression with all-cause, cancer-related, and noncancer-related mortality among 5-year cancer survivors: a population-based cohort study. Sci Rep, 2019. 9(1): p. 18334.
Strine, T.W., et al., The association of depression and anxiety with obesity and unhealthy behaviors among community-dwelling US adults. Gen Hosp Psychiatry, 2008. 30(2): p. 127-37.
Ostovar, S., et al., Prevalence of psychological distress among cancer patients in Southeast Asian countries: A systematic review. Eur J Cancer Care (Engl), 2022. 31(6): p. e13669.
Heo, J., et al., Psychiatric comorbidities among breast cancer survivors in South Korea: a nationwide population-based study. Breast Cancer Res Treat, 2017. 162(1): p. 151-158.
Lee, H.J., et al., The Positive Effects of Cancer Survivor Support Service on Distress in South Korea: A Nationwide Prospective Study. Front Med (Lausanne), 2022. 9: p. 769221.
Turner, J., S. Wooding, and C. Neil, Psychosocial impact of breast cancer: a summary of the literature 1986-1996. 1998.
Pinquart, M. and P.R. Duberstein, Depression and cancer mortality: a meta-analysis. Psychol Med, 2010. 40(11): p. 1797-810.

No competing interests reported.

Supplementarytable.docx

Download PDF

Version 1

posted

You are reading this latest preprint version

Depression and Long-term Mortality among 5-year Breast Cancer Survivors in Korea: A Population-based Cohort Study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

INTRODUCTION

METHODS

Data Source

Study Population and Design

Key variables

Statistical analysis

RESULTS

Baseline Characteristics

Depression in survivor period and mortality Outcomes among 5-year survivors breast cancer patients

Stratified analysis

DISCUSSION

Limitations

Conclusions

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1