Introduction
The COVID-19 pandemic is having a major impact on global health. During the early months of the COVID-19 pandemic in the Netherlands, a 46% decline in general practitioner consultations, and a sharp decrease in cancer diagnoses were reported [
1,
2]. Increased (perceived) thresholds to health care access may negatively affect patients’ (psycho)social and physical well-being as well as their prognosis.
Symptoms of anxiety and depression among cancer patients and survivors have been reported to affect their health care behavior and health care consumption during a health threat of the magnitude of COVID-19 [
3].
The aim of this study was to assess the prevalence of anxiety and depression among a large cohort of breast cancer patients and survivors during the COVID-19 pandemic. In addition, we assessed the association between the presence of symptoms of anxiety and/or depression and COVID-19-specific concerns, including health care behavior and consumption.
Materials and methods
The present study was conducted within the prospective observational multicenter 'Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion' (UMBRELLA), including patients with histologically proven invasive breast cancer or ductal carcinoma in situ (DCIS) referred from regional and tertiary referral hospitals to the University Medical Center Utrecht (UMCU) for adjuvant radiation therapy [
4,
5]. All participants completed self-reported UMBRELLA questionnaires, including the Hospital Anxiety and Depression Scale (HADS), at regular time intervals during and after their breast cancer treatment.
All active participants, who enrolled in the UMBRELLA cohort between October 2013 and April 2020 and consented to receiving online questionnaires, were sent a survey (April 7, 2020), including the HADS and COVID-19-related questions [
6,
7]. Ethical approval was obtained from the Medical Ethics Committee of the UMCU (NL52651.041.15, METC 15/165). The UMBRELLA study is registered on clinicaltrials.gov (NCT02839863).
HADS is a 14-item questionnaire using a 4-point Likert scale. Scores ≥ 12 on the total HADS, and scores ≥ 8 on the 7-item anxiety and depression subscales indicated increased risk of depression or anxiety disorder [
8].
Demographic and clinical data, including age, highest educational level, type of surgery, most invasive axillary treatment, (neo-)adjuvant systemic treatment, radiotherapy, and pathological T and N stage (AJCC 7th edition), were collected in the context of UMBRELLA and provided by the Netherlands Cancer Registry (NKR) [
9].
Frequencies, proportions, means with standard deviation, or medians with interquartile ranges were used to describe patient demographics, treatment characteristics and HADS scores. A Chi-square test was performed to compare differences in proportions of patients scoring above the clinically relevant HADS threshold scores before and during COVID-19 [
10]. Univariable and multivariable logistic regression analyses were used to evaluate to what extent relevant clinical demographic, tumor- and treatment characteristics affected clinically relevant symptoms of anxiety and/or depression during COVID-19. Two-sided
p values < 0.05 were considered statistically significant. Statistical analyses were performed with IBM Statistical Package for Social Sciences (SPSS) software, version 25 (IBM Corp, Armonk, NY).
Results
Of the 3239 participants enrolled in the UMBRELLA cohort between October 2013 and April 2020, 1595 participants met the inclusion criteria. Of those, 1051 (66.0%) participants completed the COVID-19-specific questionnaire, of which 4.9% (n = 51) were under active treatment for their breast cancer.
Prevalence and risk factors for anxiety and/or depression during COVID-19
Overall, 284 (27.0%) participants experienced clinically relevant symptoms of anxiety and/or depression during COVID-19 (Table
1). Of all participants who experienced symptoms of anxiety and/or depression during COVID-19, 62.7% (
n = 156) already experienced these symptoms pre-COVID-19. A total of 18.2% (
n = 191) of all participants reported symptoms of anxiety and 16.0% (
n = 168) symptoms of depression during the pandemic. The proportion of participants experiencing symptoms of anxiety and/or depression was slightly, but significantly lower before the pandemic (23.4%,
n = 220).
Table 1
Baseline characteristics of participants with or without a clinically relevant increase in total HADS score (≥ 12), i.e., symptoms of anxiety and/or depression, as measured by the HADS questionnaire during the COVID-19 pandemic (n = 1051)
Patient characteristics | | | | | |
Age in years at inclusion, mean (SD) | 57 | 9.6 | 55 | 10.1 | 0.003 |
Sex, No. (%) | | | | | 0.135 |
Female | 761 | 99.2 | 284 | 100.0 | |
Male | 6 | 0.8 | 0 | 0.0 | |
Highest educational level | | | | | 0.185 |
Primary or (post-)secondary school | 326 | 42.5 | 133 | 46.8 | |
College or university | 434 | 56.6 | 147 | 51.8 | |
Unknown | 7 | 0.9 | 4 | 1.4 | |
Time since diagnosis (months), median (IQR) | 24 | 6–42 | 24 | 6–42 | 0.859 |
Unknown, No. (%) | 6 | 0.8 | 3 | 1.1 | |
Tumor characteristics | | | | | |
Pathological T stadium | | | | | 0.698 |
In situ (IS), 0, I or II | 698 | 91.0 | 256 | 90.1 | |
III or IV | 15 | 2.0 | 8 | 2.8 | |
X or unknown | 54 | 7.0 | 20 | 7.0 | |
Pathological N stadium | | | | | 0.005 |
0 | 461 | 60.1 | 145 | 51.1 | |
I, II or III | 198 | 25.8 | 102 | 35.9 | |
X or unknown | 108 | 14.1 | 37 | 13.0 | |
Treatment characteristics | | | | | |
Type of breast surgery | | | | | 0.112 |
Breast conserving therapy | 596 | 77.7 | 217 | 76.4 | |
Mastectomy | 70 | 9.1 | 24 | 8.5 | |
Mastectomy with direct breast reconstruction | 65 | 8.5 | 28 | 9.9 | |
No breast surgery | 0 | 0.0 | 2 | 0.7 | |
Unknown | 36 | 4.7 | 13 | 4.6 | |
Most invasive axillary treatment | | | | | 0.509 |
Sentinel node procedure | 572 | 74.6 | 212 | 74.6 | |
Axillary lymph node dissectionb | 56 | 7.3 | 26 | 9.2 | |
Unknown or not performed | 139 | 18.1 | 46 | 16.2 | |
Systemic therapyc | | | | | 0.008 |
No systemic therapy | 168 | 21.9 | 38 | 13.4 | |
Chemotherapyd | 261 | 34.0 | 117 | 41.2 | |
Endocrine therapy or immunotherapy | 102 | 13.3 | 45 | 15.8 | |
Unknown | 236 | 30.8 | 84 | 29.6 | |
Radiation therapy | | | | | 0.003 |
Local | 515 | 67.1 | 163 | 57.4 | |
Locoregionale | 158 | 20.6 | 86 | 30.3 | |
No radiation therapy or type unknown | 94 | 12.3 | 35 | 12.3 | |
Currently receiving active breast cancer treatmentf | | | | | 0.779 |
Yes | 37 | 4.8 | 14 | 4.9 | |
No | 723 | 94.3 | 266 | 93.7 | |
Other | 7 | 0.9 | 4 | 1.4 | |
Hospital Anxiety and Depression Scale | | | | | |
Total HADS score before COVID-19a,g | | | | | < 0.001 |
Above threshold | 64 | 9.3 | 156 | 62.7 | |
Below threshold | 627 | 90.7 | 93 | 37.3 | |
HADS anxiety score before COVID-19a,g | | | | | < 0.001 |
Above threshold | 57 | 8.2 | 124 | 49.8 | |
Below threshold | 634 | 91.8 | 125 | 50.2 | |
HADS depression score before COVID-19a,g | | | | | < 0.001 |
Above threshold | 26 | 3.8 | 89 | 35.7 | |
Below threshold | 665 | 96.2 | 160 | 64.3 | |
Lower age, higher pathological N stage, receipt of systemic therapy or radiotherapy and pre-existent symptoms of anxiety or depression were significantly associated with anxiety and/or depression during COVID-19 (Table
1). In multivariable analysis, only pre-existent symptoms of anxiety or depression were independently and significantly associated with symptoms of anxiety and/or depression during COVID-19 (OR 6.1, 95%CI 4.1–9.2 and OR 6.0, 95% CI 3.5–10.2, resp., Table
2).
Table 2
Multivariable logistic regression analysis of risk factors for clinically relevant increase in symptoms of anxiety and/or depression, i.e., total HADS score above threshold (≥ 12), during the COVID-19 pandemic (n = 940)
Age | 0.99 | 0.97–1.01 |
Pathological N stadium | | |
0 | Ref. | |
I, II or III | 1.12 | 0.67–1.85 |
X or unknown | 1.36 | 0.75–2.45 |
Systemic therapya | | |
No systemic therapy | Ref. | |
Chemotherapyb | 1.48 | 0.85–2.55 |
Endocrine therapy or immunotherapy | 1.55 | 0.83–2.88 |
Unknown | 1.41 | 0.81–2.44 |
Radiation therapy | | |
Local | Ref. | |
Locoregionalc | 1.49 | 0.89–2.51 |
No radiation therapy or type unknown | 0.83 | 0.45–1.55 |
HADS anxiety score before COVID-19a | | |
Below threshold | Ref. | |
Above threshold | 6.12 | 4.05–9.24 |
HADS depression score before COVID-19a | | |
Below threshold | Ref. | |
Above threshold | 5.95 | 3.48–10.18 |
COVID-19-specific concerns and health care consumption
Significantly more participants with anxiety and/or depression experienced higher barriers to contact their general practitioner (47.5% vs. 25.0%, resp.) and breast cancer physicians (26.8% vs. 11.2%, resp.) compared to patients without these symptoms (Table
3). In addition, a higher proportion of participants with anxiety and/or depression reported that their current treatment or (after)care was affected by COVID-19 compared to those without these symptoms (32.7% vs. 20.5%, resp.).
Table 3
Patient-reported outcomes of COVID-19-specific concerns in the early months of the COVID-19 pandemic in the Netherlands (n = 1051)
Are/were you infected by the COVID-19? | | | | | 0.368 |
Yes, confirmed by nasopharyngeal swab | 1 | 0.1 | 0 | 0.0 | |
Possibly, I have or had fever | 66 | 8.6 | 34 | 12.0 | |
No, I was tested negative | 7 | 0.9 | 2 | 0.7 | |
No, I had/have no symptoms and I was not tested | 693 | 90.4 | 248 | 87.3 | |
Is the current COVID-19 measure affecting your current treatment or aftercare? | | | | | < 0.001 |
Yes | 184 | 24.0 | 102 | 35.9 | |
No | 583 | 76.0 | 182 | 64.1 | |
Do you expect that the current COVID-19 measures will affect your treatment or aftercare in the future? | | | | | < 0.001 |
Yes | 157 | 20.5 | 93 | 32.7 | |
No | 610 | 79.5 | 191 | 67.3 | |
Did the threshold to contact your general practitioner change, because of the COVID-19 situation? | | | | | < 0.001 |
Yes, I contact my general practitioner more easily | 13 | 1.7 | 6 | 2.1 | |
Yes, I contact my general practitioner less easily | 192 | 25.0 | 135 | 47.5 | |
No | 562 | 73.3 | 143 | 50.4 | |
Did the threshold to contact the physicians treating your breast cancer change, because of the COVID-19 situation? | | | | | < 0.001 |
Yes, I contact my breast cancer physicians more easily | 7 | 0.9 | 1 | 0.4 | |
Yes, I contact my breast cancer physicians less easily | 86 | 11.2 | 76 | 26.8 | |
No | 674 | 87.9 | 207 | 72.9 | |
Discussion
During the COVID-19 pandemic, 27.0% of the (ex-)breast cancer patients reported clinically relevant symptoms of anxiety and/or depression. (Ex-)breast cancer patients with anxiety and/or depression reported to experience higher thresholds to contact their health care providers. Factors independently associated with anxiety and/or depression during COVID-19 were pre-existent symptoms of anxiety or depression.
In the early months of the COVID-19 pandemic, a sharp decrease in cancer diagnoses and a 46% decline in general practitioner consultations were observed in the Netherlands [
1,
2]. In this study, participants with anxiety and/or depression reported higher barriers to contact their health care providers during COVID-19 compared to those without these symptoms. The COVID-19 pandemic might have increased the perceived burden on patients with symptoms of anxiety and/or depression. High levels of anxiety and perceived threat have been shown to be related to increased avoidance behavior [
11]. Anxiety for a COVID-19 infection, a higher level of moral concerns about wasting the physicians’ time for non-COVID-19-related symptoms, and assumptions about scarcity in the capacity of health care services for non-COVID-19-related care might also explain these barriers in seeking health care among patients with symptoms of anxiety and/or depression [
1]. These results suggest that, in case of subsequent waves or a future pandemic, (ex-)breast cancer patients experiencing anxiety and/or depression are especially at risk for reduced health care consumption and may need extra encouragement to contact their health care providers, when necessary.
The proportion of participants experiencing anxiety and/or depression increased only slightly during COVID-19 (27.0%), when compared to pre-COVID-19 (23.4%). However, there was a considerable shift: quite some patients with pre-existing symptoms of anxiety and/or depression no longer experienced clinically relevant levels of anxiety and/or depression during COVID-19 and vice versa. The participants’ perception of the COVID-19 pandemic and different coping mechanisms might play a role in this shift [
11]. Higher tolerance for uncertainty is related to better coping strategies and lower threat appraisal. For example, patients who tolerated uncertainty better, experienced lower levels of anxiety during the H1N1 pandemic in 2009 and showed higher levels of problem-focused coping [
11]. However, further studies are needed to better understand these coping mechanisms in the context of a major health threat, and their effect on health care consumption.
Our findings that 18.2% of all participants reported symptoms of anxiety and 16.0% symptoms of depression, are in line with outcomes previously reported among UMBRELLA participants with early invasive breast cancer or DCIS prior to COVID-19 at 24 months after diagnosis (anxiety 12.5–17.1%, depression 6.0–16.1%) [
12]. Moreover, the observed proportion of (ex-)breast cancer patients with anxiety and/or depression during COVID-19 seemed even lower when compared to the general population. A recent meta-analysis assessing anxiety and depression among a general population in Europe during COVID-19 observed that 32.4% (
n = 8.341) experienced symptoms of anxiety and 23.8% (
n = 8.341) symptoms of depression [
13].
Although previous research showed that mental health can be impaired in the context of a major health threat, there are still insufficient clinical (screening) tools that can help identify those at risk [
14]. Pre-existent anxiety and/or depression was reported by 62.7% (
n = 156) of the participants with anxiety and/or depression during COVID-19. Similarly, a recent global study among non-cancer patients with pre-existent anxiety or depression (
n = 2.734) reported worsening of psychological well-being in at least 50.0% during COVID-19 [
15].
With the aim of providing adequate (mental) health support in the context of a health threat of this magnitude, surveillance and clear documentation of symptoms of anxiety and/or depression prior to and during major health threats seem a valuable tool to identify those at risk for reduced health care consumption. Especially in times of lockdown and social distancing, integration of e-mental health applications and digital psychological interventions is important to improve supportive care for those at risk. Last, raising public awareness about the importance of encouraging these particularly vulnerable individuals to contact their health care professionals, when necessary, is warranted.
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